Sugi Variant

Sugi Variant/MSH4

MSH4 — 157 ClinVar variants

All ClinVar germline MSH4 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 127 flagged for review →

7 Pathogenic · 1 Pathogenic/Likely pathogenic · 9 Likely pathogenic · 2 Conflicting · 8 Benign · 4 Likely benign · 126 Uncertain significance

Full MSH4 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 127

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 2

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

Predictors agree, ClinVar conflicts 2

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

Predictors lean, ClinVar uncertain 102

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

Predictors split 21

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

All MSH4 variants

Pathogenic 7

  • c.2355+1G>A No assertion criteria premature ovarian failure 20
  • p.Arg910Ter No assertion criteria Genetic non-acquired premature ovarian failure
  • p.Asp727fs No assertion criteria spermatogenic failure 2
  • p.Gln518Ter No assertion criteria spermatogenic failure 2
  • p.Lys741fs No assertion criteria Genetic non-acquired premature ovarian failure
  • p.Trp650Ter No assertion criteria spermatogenic failure 2
  • p.Val269fs No assertion criteria spermatogenic failure 2

Pathogenic/Likely pathogenic 1

Likely pathogenic 9

  • p.Arg78fs Single submitter premature ovarian failure 20
  • p.Gln485Ter Single submitter Non-obstructive azoospermia
  • p.Lys562_Val563insTer Single submitter Non-obstructive azoospermia
  • p.Pro880fs Single submitter premature ovarian failure 20
  • p.Ser733Ter Single submitter Non-obstructive azoospermia
  • p.Ile355Val No assertion criteria Genetic non-acquired premature ovarian failure ⚠
  • p.Met619Val No assertion criteria Genetic non-acquired premature ovarian failure ⚠
  • p.Thr342Ile No assertion criteria Genetic non-acquired premature ovarian failure
  • p.Thr792Ala No assertion criteria Genetic non-acquired premature ovarian failure

Conflicting classifications of pathogenicity 2

Benign 8

Likely benign 4

Uncertain significance 126