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Blood Test Tracker

MTHFR A1298C

A gene test for a common MTHFR variant that appears milder than C677T. Medical groups advise against routine testing for clots, and most people with it are healthy.

AI-verified against cited sources. Awaiting expert reviewAlso called A1298C, 1298A>CLOINC 28060-2

What it is

MTHFR is a gene that makes an enzyme your body uses to handle folate (vitamin B9) and homocysteine. The A1298C variant is common and is thought to lower the enzyme's activity less than the better-known C677T variant. You get one copy of the gene from each parent, so the result is AA (no copies of the variant), AC (one copy) or CC (two copies). Some labs call it a mutation, but it is an ordinary variation. It is a one-time DNA test, and the result never changes.

Why it matters

People are often tested because of worries about blood clots, pregnancy loss or folate. The American College of Medical Genetics and Genomics (ACMG) says MTHFR testing should not be part of a routine work-up for clotting problems, and the American Society of Hematology lists MTHFR variants among changes shown not to be linked to blood clots in the veins. A homocysteine or folate blood test usually tells you more about what is happening in your body now. Most people with AC or CC are healthy.

If it’s high

An AC or CC result means you carry one or two copies of a common variant. The ACMG describes two copies of A1298C (CC) as unlikely to be clinically significant, and the same goes for having one copy of A1298C together with one copy of C677T. The American Society of Hematology says this variant has been shown not to be linked to blood clots in the veins, and most people with this result have no health problems. If your report also shows two copies of C677T, ask your clinician what that combination means for you.

Common causes

  • You inherited the variant from one or both parents. It is common.

What can help

  • Ask your clinician whether a homocysteine blood test would tell you more than the gene result
  • Get folate from food, such as dark green leafy vegetables, beans and peas, citrus fruit, and fortified breads and cereals
  • If you could become pregnant, ask your clinician about folic acid, which is advised before and during pregnancy whether or not you have this variant
  • Tell your care team about your result if you are ever offered a medicine that works through folate, such as methotrexate

What can affect your result

  • Having C677T as well: the two variants are rarely on the same copy of the gene, so a person with one copy of each usually has one on each copy
  • Folate intake and fortified foods change blood folate and homocysteine more than this gene does
  • Some lab reports print both MTHFR variants (C677T and A1298C) on one line. They are separate results.
  • The test reads your DNA, so fasting, medicines, pregnancy and illness do not change it
  • Diet, fasting, folate supplements and medicines do not change this result, because the test reads inherited DNA. Blood folate and homocysteine levels do respond to diet and supplements, but the gene result does not.
  • Some reports print both MTHFR variants (C677T and A1298C) on one line, and LOINC has a combined code for that (94414-0). They are two separate results.
  • A previous bone marrow (stem cell) transplant from a donor could affect any DNA test on blood, because the DNA may come from the donor's cells.

The result does not change over time, because it reflects DNA you inherited.

When to talk to a clinician

An AC or CC result is not an emergency and does not mean you will have a clot. Whatever your result, call 911 or your local emergency number for chest pain, trouble breathing, coughing up blood or fainting, and contact a clinician promptly if one leg or arm becomes red, warm, swollen or painful.

Questions you could ask

  • Why was this test ordered for me, and what decision would it help with?
  • Does this result change anything about my care, or is it just background information?
  • Would a homocysteine or folate blood test tell us more than this gene result?
  • If I could become pregnant, what should I know about folate and this result?

Questions people ask

Is A1298C worse than C677T?

No. The ACMG says A1298C has been studied less, but the evidence so far suggests it is milder than C677T.

I have one copy of A1298C and one copy of C677T. Is that a problem?

The ACMG considers this combination (called a compound heterozygote) unlikely to be clinically significant. Your clinician can look at it together with your homocysteine level, your symptoms and your family history.

Do I need to avoid folic acid or take a special form of folate because of MTHFR?

The CDC says people with an MTHFR variant can process all types of folate, including folic acid, and that how much folic acid you get matters more for your blood folate than your genotype does. If you are thinking about supplements, especially if you could become pregnant, ask your clinician what is right for you.

Show the science and sources

For clinicians and researchers

A1298C (rs1801131) is c.1286A>C, p.Glu429Ala in current notation, a missense change in MTHFR. The ACMG 2013 statement says both this variant and C677T (c.665C>T) are known to decrease enzyme activity, but that A1298C has been studied less and current evidence suggests it is milder than the thermolabile C677T variant. The two variants are in linkage disequilibrium, so people with both are usually compound heterozygotes in trans, and homozygosity for one variant with heterozygosity for the other is rare. ACMG considers the C677T heterozygote, the A1298C homozygote and the C677T/A1298C compound heterozygote unlikely to be clinically significant; the rare 'triple variant' genotypes may carry risk but that is described as speculative, and combined genotypes were not significantly different from controls in preliminary findings. The ACMG statement was reaffirmed in April 2020 and reclassified as a Clinical Practice Resource because it no longer meets the criteria for an evidence-based guideline. ASH 2023 leaves MTHFR c.677C>T and c.1298A>C out of thrombophilia testing because they are not associated with VTE. CDC states that people with MTHFR variants can process all forms of folate, including folic acid. LOINC 28060-2 is the single-variant result; 94414-0 is a combined C677T and A1298C result, which should be split into two markers.

LOINC 28060-2 (primary), 94414-0, 21709-1. Specimen: whole-blood.

Sources

  1. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing, Genetics in Medicine (2013)
  2. Addendum: ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing, Genetics in Medicine (2020)
  3. American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing, Blood Advances (2023)
  4. MTHFR gene, MedlinePlus Genetics, National Library of Medicine
  5. MTHFR Gene Variant and Folic Acid Facts, Centers for Disease Control and Prevention (2026)
  6. Folic acid in diet, MedlinePlus Medical Encyclopedia, National Library of Medicine
  7. rs1801131 (MTHFR c.1286A>C, p.Glu429Ala), NCBI dbSNP

AI-verified against cited sources. Awaiting expert review. Last reviewed 2026-10-03. How we build and check these pages.

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