MTHFD1 Variant rs2236225: Health Risks and How to Reduce Them

Last reviewed: May 12, 2026 Last updated: May 12, 2026

Written by: Jay Hastings , CEO of PlexusDx

Jay Hastings is the CEO of PlexusDx, a precision health company focused on genetic testing, blood biomarker insights, and personalized wellness recommendations. He has more than 20 years of experience across healthcare innovation, genomics, laboratory operations, healthcare investing, and strategic finance. His work has included scaling healthcare startups, leading CLIA lab integrations, and helping expand consumer access to precision health tools.

Medically reviewed by: Jayden Lee, PharmD, EMBA

Jayden Lee, PharmD, EMBA, is the PlexusDx Medical Science Liaison with a PharmD and MBA specializing in pharmacogenomics and clinical product development, with a proven ability to bridge the gap between genomic research and practical patient outcomes. Dr. Lee has more than 10 years of professional experience in clinical pharmacy, academia, and research.

This article is part of the PlexusDx Education Hub — your resource for evidence-based guidance on methylation & mthfr. Browse all Methylation & MTHFR education

Deep in the machinery your cells use to build DNA, process folate, and run methylation sits a gene called MTHFD1. A common variant of this gene, rs2236225 (also written as G1958A or the R653Q change), can subtly shift how efficiently your body handles folate and choline — two nutrients central to development, brain health, and cardiovascular biology. If your genetic report flags this variant, it is worth understanding what it does, what it is associated with, and how nutrition and a provider can help you support the pathway.

What MTHFD1 Does in One-Carbon Metabolism

MTHFD1 encodes a three-in-one enzyme that carries out several steps of what scientists call one-carbon metabolism — the network that shuttles single carbon atoms around to build the raw materials for DNA and RNA and to power methylation. Methylation, in turn, is how the body switches genes on and off, processes homocysteine, and makes key molecules like creatine and phospholipids. MTHFD1 also links folate metabolism to the demand for choline, because when folate-based pathways are strained, the body leans more heavily on choline as an alternative methyl source.

The rs2236225 Variant Explained

The rs2236225 variant swaps a single DNA base, changing the enzyme so that one of its activities works a little less efficiently. The A allele (the R653Q form) is common in many populations, so carrying it is not rare or inherently alarming. What it can do is make the folate-to-choline handoff less flexible: people with the variant may have a higher functional demand for dietary choline, especially during periods of high biological need. This is a tendency, not a diagnosis — many carriers stay well nourished without ever noticing an effect.

Health Associations Studied for This Variant

Research has connected the MTHFD1 rs2236225 variant to a modestly increased risk of neural tube defects in pregnancy, particularly when maternal folate or choline intake is low, which is one reason adequate folate before and during pregnancy is broadly recommended. Some studies have also examined links to choline deficiency, altered homocysteine handling, and folate-dependent processes. These associations are population-level and depend heavily on diet and other genes — including well-known methylation genes like MTHFR and PEMT, which also influence choline demand. The variant raises the importance of nutrient status; it does not cause disease on its own.

Choline and Folate: The Nutrient Connection

Because MTHFD1 sits at the crossroads of folate and choline, the practical story often comes down to nutrition. Folate is found in leafy greens, legumes, and fortified grains; choline is concentrated in eggs, liver, and to a lesser degree fish, meat, and cruciferous vegetables. Many people fall short of recommended choline intake regardless of genotype, and a variant like rs2236225 can make that gap more meaningful. Whether supplementation is appropriate — and at what level — is an individual decision that belongs with a qualified provider, especially during pregnancy.

How to Support the Pathway

You cannot change your MTHFD1 genotype, but you can support the biology around it. Broadly, that means eating a diet with reliable sources of folate and choline, discussing folate status before pregnancy, and working with a clinician or dietitian to interpret any related lab work, such as homocysteine. Genetic insight is most useful as a prompt for these conversations — not as a self-directed treatment plan. The goal is to turn a genetic tendency into an informed nutrition and monitoring strategy tailored to you.

What Genetic Insight Adds

Knowing you carry MTHFD1 rs2236225 does not diagnose, treat, or prevent any condition. It adds pathway-level context about folate and choline metabolism that you can bring to a provider. The Precision Peptide Genetic Test analyzes your DNA across 14 pathways, 49 peptides, 150+ genetic insights, mapping methylation and metabolic pathways so you can understand your tendencies rather than guess at them. PlexusDx tells you about your biology; it does not tell you what to put in your body. Insight first, decisions with a clinician second.

Frequently Asked Questions

What does the MTHFD1 rs2236225 variant do?

The rs2236225 variant (R653Q) slightly reduces the efficiency of the MTHFD1 enzyme in one-carbon metabolism, the network that supports DNA synthesis, folate processing, and methylation. Carriers may have a higher functional demand for dietary choline. It is a common variant and a tendency, not a diagnosis or a disease.

How can I reduce risks linked to this variant?

You cannot change the gene, but you can support the pathway with reliable dietary folate and choline — leafy greens, legumes, eggs, and fortified foods — and by discussing folate status before pregnancy. A provider or dietitian can interpret related labs like homocysteine and advise whether supplementation makes sense for you.

Is MTHFD1 the same as MTHFR?

No, they are different genes, but both work in methylation and one-carbon metabolism, so they are often discussed together. MTHFR affects folate activation, while MTHFD1 handles later folate-dependent steps and links folate to choline demand. Variants in either can influence homocysteine and nutrient needs.

Does a genetic test diagnose choline deficiency?

No. A genetic test does not diagnose choline deficiency or any condition. It provides pathway-level context — for example, that an MTHFD1 variant may raise your choline demand. Actual nutrient status is assessed through diet review and clinical labs interpreted by a qualified healthcare provider.

Curious how your own biology fits the picture? Take the Precision Peptide Genetic Test to see pathway-level context drawn from your DNA — then bring those insights to a conversation with your provider. Test before you invest.

This article is part of the PlexusDx Education Hub. Browse all Methylation & MTHFR education

The Precision Peptide Genetic Test analyzes how your genes influence peptide-related biological pathways. It does not recommend, prescribe, or determine which peptides you should use, and it does not diagnose, treat, cure, or prevent any condition. Consult a qualified healthcare provider before beginning any peptide protocol or making changes to your care.

Medical and Editorial Standards

Medical review process: This article was reviewed for medical accuracy, scientific clarity, evidence alignment, and appropriate discussion of genetics, medications, supplements, biomarkers, and health-related claims.

Sources and evidence: PlexusDx educational content is developed using peer-reviewed research, clinical literature, reputable medical references, and, where applicable, public health or regulatory guidance. References are included at the end of the article when scientific, medical, or health-related claims are discussed.

Commercial transparency: PlexusDx offers genetic testing, blood biomarker testing, personalized supplement recommendations, and related precision wellness services. Product mentions are intended to help readers understand available options and should not be interpreted as medical advice.

Important disclaimer: PlexusDx educational content is for informational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before making decisions about medications, supplements, genetic testing, lab testing, or health-related care.