MTHFR rs2274976: What Your Genotype Means
The rs2274976 variant is a genetic change located within the MTHFR gene, which plays a key role in how the body processes folate. Research has investigated this variant as a potential factor in folate-sensitive health outcomes, though its clinical impact is generally considered limited.
What each genotype means
Common genetic profile
This is the most common genotype observed in many populations. Research into this specific variant is limited, and there is no clear evidence that this genotype significantly alters MTHFR enzyme function or health outcomes.
This is the most frequent genotype globally, representing the majority of individuals in most studied populations.
Common genetic profile
This genotype represents a heterozygous state for this variant. Current scientific literature does not establish a definitive clinical impact for this genotype, and it is generally considered to have no significant effect on folate metabolism or related health risks.
This genotype is found in a significant portion of the population, with the minor allele frequency for this variant reported at approximately 5%.
Variant genetic profile
This genotype represents the homozygous state for the minor allele. While some studies have explored its potential association with specific conditions like nonsyndromic cleft lip or palate in certain populations, the evidence remains limited and inconsistent across different ethnic groups.
This is the least common genotype, occurring in a small percentage of the population consistent with the minor allele frequency of approximately 5%.
Understanding the rs2274976 Variant
The rs2274976 variant is a single nucleotide polymorphism (SNP) found within the MTHFR gene. In genetics, a SNP represents a variation at a single position in the DNA sequence. For rs2274976, the variation involves a change between the nucleotides guanine (G) and adenine (A). This variant is cataloged in major genetic databases, including dbSNP and ClinVar, and is one of many variations identified within the MTHFR gene. While the MTHFR gene is most famous for its more common variants like C677T, rs2274976 is specifically tracked to understand its unique contribution to the gene's overall function. Scientists study these positions to determine if they alter the structure or efficiency of the proteins the body produces, which in turn can influence various metabolic pathways.
The Role of the MTHFR Gene
The MTHFR gene provides the instructions for the body to create the methylenetetrahydrofolate reductase enzyme. This enzyme is essential for the folate cycle, a biological process that converts folate (vitamin B9) into its active form, 5-methyltetrahydrofolate. This active form is necessary for the body to process homocysteine, an amino acid, into methionine, which is required for DNA synthesis and protein methylation. When the MTHFR enzyme functions optimally, it helps maintain healthy levels of homocysteine in the blood. If the enzyme's activity is reduced, it can potentially lead to an accumulation of homocysteine. Because folate is critical for cell division and development, the MTHFR gene is a frequent subject of research regarding how genetic differences might influence nutritional requirements and long-term health.
Research and Clinical Associations
Research into rs2274976 has explored its potential association with various health conditions, including neural tube defects and other pregnancy-related outcomes. Some studies have suggested that this variant may act as a risk marker in specific populations, such as in cases of nonsyndromic cleft lip or palate. However, it is important to note that the evidence strength for these associations is generally considered limited. Many studies show mixed results, and the clinical effects of this specific variant are often small. It is not a diagnostic marker for disease, and having a particular genotype does not guarantee a specific health outcome. Current scientific consensus emphasizes that environmental factors, such as adequate dietary folate intake, are often more significant in determining blood folate levels and overall health than the presence of a single MTHFR variant.
Population Frequency
The frequency of the rs2274976 minor allele varies significantly across different ancestral groups. Data indicates that the minor allele frequency (MAF) is roughly 1–20% depending on the population studied. This variation is common in human genetics, where certain alleles become more or less prevalent due to historical migration and evolutionary pressures. Because the frequency is not uniform, the likelihood of carrying the A allele differs depending on an individual's genetic background. Understanding these population-level differences is a core component of genomic research, as it helps scientists distinguish between common variations that are part of normal human diversity and those that might have more specific clinical implications.
Interpreting Your Genetic Information
If you have received information about your rs2274976 genotype, it is important to view it within the context of your overall health. This variant is not a standalone predictor of disease, and the scientific evidence linking it to specific health outcomes remains limited. You cannot use this information to diagnose yourself or to make medical decisions, such as changing your diet or starting supplements, without professional guidance. If you are concerned about your folate levels or pregnancy health, the most effective approach is to consult with a healthcare provider or a registered dietitian. They can assess your nutritional status, medical history, and lifestyle to provide personalized recommendations. Always discuss any changes to your health regimen with a clinician to ensure they are safe and appropriate for your individual needs.
How common is this variant?
The minor allele frequency for rs2274976 is approximately 1–20%, with significant variation observed across different global ancestral populations.
Frequently asked questions
Is rs2274976 the same as the MTHFR C677T mutation?
No, rs2274976 is a different genetic variant than the well-known C677T (rs1801133) variant. While both are located in the MTHFR gene, they are distinct positions in the DNA sequence with different research histories.
Should I take extra folate if I have the A/A genotype?
You should not make changes to your supplement routine based on a single genetic variant. Please consult with your doctor or a registered dietitian to determine if your folate intake is appropriate for your specific health needs.
Does this variant cause health problems?
The evidence linking rs2274976 to specific health problems is limited and often mixed. It is not considered a direct cause of disease, and most people with this variant live healthy lives.
Where can I find more information about my MTHFR results?
You can discuss your genetic reports with a certified genetic counselor or your primary care physician. They can help you interpret your results in the context of your overall health and family history.
Sources & further reading
Educational information only, last refreshed 10/1/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Functional polymorphism influencing homocysteine dynamics and vascular endothelial recovery during high-intensity training.
Missense variant influencing folate metabolic pathway activity and baseline plasma homocysteine levels.
This variant in the MTHFR gene is linked to altered folate metabolism and mild hyperhomocysteinemia.
The MTHFR c.1298A>C (p.Glu429Ala) missense variant causes a modest reduction in enzyme activity, but major clinical consensus guidelines and recent GWAS indicate it has no independent clinical significance for thrombophilia or folate biomarker deficiency in isolation.
The MTHFR 677C>T (Ala222Val) missense variant encodes a thermolabile enzyme with reduced catalytic activity, leading to mildly elevated plasma homocysteine levels particularly when folate status is suboptimal, though major professional genetics guidelines advise against routine clinical testing for cardiovascular disease or thrombophilia.
Rare functional missense variant in MTHFR (p.Arg157Gln) associated with reduced folate pathway enzyme activity and hyperhomocysteinemia.