MTHFS — 56 ClinVar variants

All ClinVar germline MTHFS variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 25 flagged for review →

4 Pathogenic · 3 Likely pathogenic · 2 Conflicting · 5 Benign · 2 Benign/Likely benign · 13 Likely benign · 27 Uncertain significance

Full MTHFS gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 25

Variants where the independent computational evidence doesn't line up with the clinical picture — a QC signal for a second look, not a reclassification.

Predictors agree, ClinVar conflicts 2

ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.

MTHFS p.Arg145Gln Conflicting Single submitter
neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination
MTHFS p.Arg84Gln Conflicting Single submitter

Predictors lean, ClinVar uncertain 19

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.

Predictors split 4

The independent predictors disagree with each other — read with care.

All MTHFS variants

Pathogenic 4

p.Ala9fs Multiple submitters neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination
p.Arg74Ter Single submitter
p.Lys106Ter Single submitter neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination
p.Leu36Pro No assertion criteria neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination

Likely pathogenic 3

p.Gln162Ter Single submitter neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination
p.Ser7fs Single submitter neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination
p.Tyr153Cys Single submitter MTHFS-related disorder

Conflicting classifications of pathogenicity 2

p.Arg145Gln Single submitter neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination ⚠
p.Arg84Gln Single submitter ⚠

Benign 5

p.Asp140= Multiple submitters
p.Ala5Val Single submitter
p.Arg34Leu Single submitter
p.Glu198Lys Single submitter
p.Thr202Ala Single submitter

Benign/Likely benign 2

c.117+7G>C Multiple submitters
p.Lys18= Multiple submitters

Likely benign 13

c.117+12C>T Single submitter
c.118-18C>T Single submitter
c.380-5C>T Single submitter
p.Ala172= Single submitter
p.Asn188= Single submitter
p.Glu28= Single submitter
p.Leu30= Single submitter
p.Lys50= Single submitter
p.Ser12Arg Single submitter
p.Ser200= Single submitter
p.Ser8Gly Single submitter
p.Thr107= Single submitter
p.Val119Leu Single submitter

Uncertain significance 27

p.Ser12Ile Multiple submitters ⚠
c.117+100C>G Single submitter neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination
c.117+6A>C Single submitter
p.Ala26Thr Single submitter ⚠
p.Ala5Ser Single submitter ⚠
p.Arg120Gln Single submitter ⚠
p.Arg14Trp Single submitter ⚠
p.Arg82Trp Single submitter ⚠
p.Arg84Trp Single submitter ⚠
p.Asp189Asn Single submitter ⚠
p.Gln32Leu Single submitter ⚠
p.Gln38Arg Single submitter ⚠
p.Gly15Arg Single submitter ⚠
p.Gly15Val Single submitter ⚠
p.Ile95Val Single submitter ⚠
p.Lys10Gln Single submitter ⚠
p.Met24Thr Single submitter ⚠
p.Met58Val Single submitter
p.Pro112Leu Single submitter ⚠
p.Pro98Leu Single submitter ⚠
p.Ser12Asn Single submitter ⚠
p.Ser25Asn Single submitter ⚠
p.Thr107Ile Single submitter ⚠
p.Thr126= Single submitter
p.Thr126Ile Single submitter ⚠
p.Thr202Ile Single submitter ⚠
p.Val35Ala No assertion criteria ⚠