Sugi Variant

Sugi Variant/VARS1

VARS1 — 341 ClinVar variants

All ClinVar germline VARS1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 213 flagged for review →

13 Pathogenic · 3 Pathogenic/Likely pathogenic · 15 Likely pathogenic · 11 Conflicting · 10 Benign · 4 Benign/Likely benign · 64 Likely benign · 221 Uncertain significance

Full VARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 213

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 vs ClinVar 4

ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.

Predictors agree, ClinVar conflicts 6

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

Predictors lean, ClinVar uncertain 137

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

Predictors split 66

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

All VARS1 variants

Pathogenic 13

  • p.Gln1155Ter Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Gln1216Ter Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Glu61Ter Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Gly380fs Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Thr535fs Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Trp417Ter Single submitter
  • c.1577-2A>G No assertion criteria neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Ala692Pro No assertion criteria neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Arg442Ter No assertion criteria neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Gly822Ser No assertion criteria neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Leu434Val No assertion criteria neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy ⚠
  • p.Leu78fs No assertion criteria neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Met1064Ile No assertion criteria neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy ⚠

Pathogenic/Likely pathogenic 3

  • p.Arg1119Cys Multiple submitters neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Arg1208Ter Multiple submitters neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Trp790Ter Multiple submitters neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy

Likely pathogenic 15

  • p.Arg1058Gln Multiple submitters neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy ⚠
  • p.Gln1039Ter Multiple submitters neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • c.2151-2A>G Single submitter
  • p.Arg618fs Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Arg942Gln Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Arg942Trp Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Arg985His Single submitter ⚠
  • p.Asn941fs Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Gln126Ter Single submitter VARS-related disorders
  • p.Glu1103Ter Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Thr1068Lys Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Thr1089Ile Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy ⚠
  • p.Thr1115Arg Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy ⚠
  • p.Pro661Thr No assertion criteria neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Ser864Ter No assertion criteria neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy

Conflicting classifications of pathogenicity 11

  • c.972+3G>A Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Arg1199Trp Single submitter Inborn genetic diseases ⚠
  • p.Arg404Trp Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy ⚠
  • p.Arg947His Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy ⚠
  • p.Leu885Phe Single submitter Abnormal brain morphology ⚠
  • p.Met447Ile Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy ⚠
  • p.Met615Val Single submitter ⚠
  • p.Phe1072Leu Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy ⚠
  • p.Pro1232= Single submitter
  • p.Thr1068Met Single submitter neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
  • p.Tyr556Asn Single submitter Inborn genetic diseases ⚠

Benign 10

Benign/Likely benign 4

Likely benign 64

Uncertain significance 221