What does MTHFR actually mean?
A thread through the evidence — ClinVar, gnomAD, ClinGen, and GTEx.
Variation
MTHFR has 1,037 variants submitted to ClinVar. Among them, 295 are classified as pathogenic or likely pathogenic, and 0 remain Variants of Uncertain Significance. Each variant is a thread in the story — some we understand, many we're still learning.
Interpretation
Interpretation of genetic variants is an evolving science. What we know about MTHFR today may shift as new evidence emerges.
Constraint
gnomAD's constraint metrics tell us how tolerant MTHFR is to different types of mutations in the general population. A LOEUF score of 0.86 suggests moderate tolerance. This is indirect evidence, but it's powerful: evolution has been running this experiment for millions of years.
Meaning
So what does it all mean? MTHFR is a gene we're still learning about. 295 variants are classified as pathogenic or likely pathogenic — evidence that's strong and actionable when it applies to you. 0 variants remain uncertain. That's the honest state of genomic medicine: if you carry a pathogenic MTHFR variant, the evidence speaks clearly. If you carry a VUS, the evidence is still accumulating. Either way, you deserve to understand what the science actually says.