Sugi Variant

Sugi Variant/SEC63

SEC63 — 565 ClinVar variants

All ClinVar germline SEC63 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 144 flagged for review →

23 Pathogenic · 7 Pathogenic/Likely pathogenic · 32 Likely pathogenic · 13 Conflicting · 77 Benign · 31 Benign/Likely benign · 133 Likely benign · 249 Uncertain significance

Full SEC63 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 144

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 1

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

Predictors agree, ClinVar conflicts 5

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

Predicted LoF vs a conflicting call 2

ClinVar submitters conflict, and it's a predicted loss-of-function change in a gene where LoF causes disease — flagged for review, not resolved (verify NMD-escape for C-terminal truncations). Non-missense.

Predictors lean, ClinVar uncertain 108

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

Predictors split 28

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

All SEC63 variants

Pathogenic 23

  • c.733+1G>A Multiple submitters polycystic liver disease 2
  • p.Trp58Ter Multiple submitters autosomal dominant polycystic liver disease
  • p.Arg37fs Single submitter
  • p.Arg45Ter Single submitter SEC63-related disorder
  • p.Asn365fs Single submitter polycystic liver disease 2
  • p.Cys341Ter Single submitter polycystic liver disease 2
  • p.Gln371Ter Single submitter
  • p.Glu352fs Single submitter
  • p.Tyr444fs Single submitter polycystic liver disease 2
  • c.514+1G>A No assertion criteria polycystic liver disease 2
  • p.Ala148fs No assertion criteria polycystic liver disease 2
  • p.Asn606fs No assertion criteria autosomal dominant polycystic liver disease
  • p.Gln322fs No assertion criteria autosomal dominant polycystic liver disease
  • p.Glu320Ter No assertion criteria autosomal dominant polycystic liver disease
  • p.Glu417Ter No assertion criteria autosomal dominant polycystic liver disease
  • p.Ile120fs No assertion criteria autosomal dominant polycystic liver disease
  • p.Lys604Ter No assertion criteria autosomal dominant polycystic liver disease
  • p.Met141fs No assertion criteria autosomal dominant polycystic liver disease
  • p.Ser526Ter No assertion criteria autosomal dominant polycystic liver disease
  • p.Thr232fs No assertion criteria autosomal dominant polycystic liver disease
  • p.Thr73_Val74insTer No assertion criteria polycystic liver disease 1
  • p.Trp212Ter No assertion criteria autosomal dominant polycystic liver disease
  • p.Trp35Ter No assertion criteria autosomal dominant polycystic liver disease

Pathogenic/Likely pathogenic 7

  • c.452+1G>A Multiple submitters polycystic liver disease 2
  • p.Arg239Ter Multiple submitters SEC63-related disorder
  • p.Arg622Ter Multiple submitters polycystic liver disease 2
  • p.Arg98Ter Multiple submitters SEC63-related disorder
  • p.His669fs Multiple submitters SEC63-related disorder
  • p.Ser632Ter Multiple submitters SEC63-related disorder
  • p.Val398fs Multiple submitters polycystic liver disease 2

Likely pathogenic 32

  • c.625-2A>G Multiple submitters polycystic liver disease 2
  • p.Asp596fs Multiple submitters polycystic liver disease 2
  • c.125_126del Single submitter polycystic liver disease 2
  • c.125-1G>A Single submitter
  • c.1440+1G>A Single submitter polycystic liver disease 2
  • c.1500+1G>A Single submitter polycystic liver disease 2
  • c.224+1G>C Single submitter SEC63-related disorder
  • c.506_514+3del Single submitter polycystic liver disease 2
  • c.829-2A>G Single submitter SEC63-related disorder
  • c.962-2A>G Single submitter polycystic liver disease 2
  • p.Arg98fs Single submitter polycystic liver disease 2
  • p.Asn582fs Single submitter
  • p.Gln229Ter Single submitter polycystic liver disease 2
  • p.Gln648Ter Single submitter polycystic liver disease 2
  • p.Glu102Ter Single submitter polycystic liver disease 2
  • p.Glu503Ter Single submitter polycystic liver disease 2
  • p.Lys402fs Single submitter SEC63-related disorder
  • p.Lys550fs Single submitter polycystic liver disease 2
  • p.Lys623fs Single submitter polycystic liver disease 2
  • p.Lys76_Ile77insTer Single submitter polycystic liver disease 2
  • p.Met479fs Single submitter SEC63-related disorder
  • p.Phe200fs Single submitter polycystic liver disease 2
  • p.Pro443fs Single submitter polycystic liver disease 2
  • p.Tyr33Ter Single submitter SEC63-related disorder
  • c.1936-2A>T No assertion criteria polycystic liver disease 2
  • p.Asp168His No assertion criteria autosomal dominant polycystic liver disease
  • p.Asp609fs No assertion criteria SEC63-related disorder
  • p.Gln375Arg No assertion criteria polycystic liver disease 2 ⚠
  • p.Gln375Pro No assertion criteria autosomal dominant polycystic liver disease
  • p.Gln543His No assertion criteria autosomal dominant polycystic liver disease ⚠
  • p.Ile120Thr No assertion criteria autosomal dominant polycystic liver disease
  • p.Val208Leu No assertion criteria autosomal dominant polycystic liver disease

Conflicting classifications of pathogenicity 13

Benign 77

Benign/Likely benign 31

Likely benign 133

Uncertain significance 249