MTHFR gene variants are inherited from your parents, not caused by anything you did or were exposed to during your lifetime. They are passed down through DNA the same way you inherit eye color or blood type. If you carry an MTHFR variant, you received it at conception, either from one parent or both.
The word “mutation” gets used a lot with MTHFR, but scientists more accurately call these changes “polymorphisms,” meaning they’re common genetic variations that don’t necessarily cause disease. They’re found in every population on Earth, and most people who carry them never develop health problems from them.
How the Variant Gets Passed Down
You have two copies of every gene, one from each parent. If one parent carries an MTHFR variant, you have a chance of inheriting one altered copy (heterozygous). If both parents carry the same variant, you could inherit two altered copies (homozygous), which has a larger effect on how the gene works.
The number of copies you inherit matters. For the most studied variant, C677T, having one altered copy reduces the enzyme’s activity to about 65% of normal. Having two altered copies drops it to roughly 30% of normal. A person with two copies of the other common variant, A1298C, retains about 60% of normal enzyme function. You can also inherit one copy of each variant from different parents, which is called being “double heterozygous” and can also reduce enzyme activity.
What Changes in the DNA
The MTHFR gene contains instructions for building an enzyme that helps your body process folate (the B vitamin). The two most common variants involve a single-letter swap in the DNA code at a specific location.
- C677T: At position 677 in the gene, the DNA letter “C” is replaced by “T.” This is the more impactful of the two variants. It produces a version of the enzyme that doesn’t work as well at higher temperatures (a property scientists call “thermolabile”).
- A1298C: At position 1298, the DNA letter “A” is replaced by “C.” This variant has a milder effect. The CDC notes there isn’t enough evidence to show it significantly affects folate processing on its own.
At least 40 other, rarer mutations in the MTHFR gene have been identified. Some of these produce a severely shortened, nonfunctional version of the enzyme and can cause a serious condition called homocystinuria. The two common variants above are far less severe.
How Common These Variants Are
MTHFR variants are remarkably widespread. The C677T variant appears in every population studied, though the frequency varies by region. In Europe, allele frequencies range from about 19% to 40%. In East Asian populations, rates are similarly high, with one study finding 33% among people in Hong Kong and 36% in Mongolia. African populations have the lowest rates, averaging around 6.6%. One indigenous Brazilian population had the highest recorded frequency at nearly 45%.
Because these variants are so common across every continent, carrying one is a normal part of human genetic diversity, not a rare defect.
What the Enzyme Actually Does
The MTHFR enzyme converts one form of folate into the form your body can actually use. That active form of folate is essential for a chemical process called methylation, which helps build DNA, regulate gene activity, and break down an amino acid called homocysteine.
When the enzyme works less efficiently, homocysteine can build up slightly in the blood. People who are homozygous for C677T (two copies) and consume the same amount of folic acid as someone without the variant have blood folate levels that are only about 16% lower on average. That’s a real difference, but it’s modest, and for most people it can be addressed by getting adequate folate through diet or supplements.
Can Anything “Activate” the Variant?
You can’t acquire an MTHFR variant during your lifetime. The DNA sequence you were born with doesn’t change. However, environmental factors can influence how actively any gene, including MTHFR, gets expressed. This field is called epigenetics.
Diet, folate intake, infections, toxic exposures, and aging can all shift how much a gene gets turned up or turned down without altering the underlying code. Research on twins has shown significant person-to-person variation in how the MTHFR gene’s activity is dialed in the brain, even between identical twins sharing the same DNA. This “epigenetic drift” tends to increase with age, meaning the practical impact of carrying an MTHFR variant may shift over time depending on your health, nutrition, and environment.
So while you can’t cause or prevent the variant itself, the degree to which it affects your body is partly shaped by factors within your control, particularly your folate and B vitamin intake.
Why the Terminology Matters
Calling MTHFR variants “mutations” can make them sound more alarming than they are. In genetics, a polymorphism is a common variation in a gene that doesn’t necessarily impair its function, while a pathogenic mutation is a change that causes disease. The C677T and A1298C variants fall into the polymorphism category. They slightly alter enzyme efficiency but do not, on their own, cause a medical condition in most people.
The practical difference is significant. A true loss-of-function mutation in MTHFR causes homocystinuria, a serious metabolic disorder. The common polymorphisms millions of people carry are not the same thing. For most carriers, maintaining adequate folate intake is enough to keep homocysteine levels and folate metabolism in a healthy range.