Sugi Variant

Sugi Variant/CLCN3

CLCN3 — 188 ClinVar variants

All ClinVar germline CLCN3 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 132 flagged for review →

3 Pathogenic · 13 Likely pathogenic · 1 Conflicting · 2 Benign · 16 Likely benign · 153 Uncertain significance

Full CLCN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 132

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 lean, ClinVar uncertain 80

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

Predictors split 50

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

All CLCN3 variants

Pathogenic 3

  • p.Asp678Ala Single submitter autism, susceptiblity to ⚠
  • p.Lys309Glu Single submitter neurodevelopmental disorder with hypotonia and brain abnormalities
  • p.Lys112fs No assertion criteria neurodevelopmental disorder with seizures and brain abnormalities

Likely pathogenic 13

  • p.Ile607Val Multiple submitters neurodevelopmental disorder with hypotonia and brain abnormalities ⚠
  • p.Thr570Ile Multiple submitters neurodevelopmental disorder with hypotonia and brain abnormalities ⚠
  • p.Val324Ala Multiple submitters neurodevelopmental disorder with hypotonia and brain abnormalities
  • p.Ala359Thr Single submitter
  • p.Asp87Val Single submitter neurodevelopmental disorder with hypotonia and brain abnormalities
  • p.Ile252Thr Single submitter neurodevelopmental disorder with hypotonia and brain abnormalities
  • p.Ile607Thr Single submitter neurodevelopmental disorder with hypotonia and brain abnormalities
  • p.Ser453Arg Single submitter neurodevelopmental disorder with hypotonia and brain abnormalities
  • p.Ser453Ile Single submitter Inborn genetic diseases
  • p.Thr514Ser Single submitter
  • p.Tyr85Cys Single submitter neurodevelopmental disorder with hypotonia and brain abnormalities
  • p.Val772Ala Single submitter neurodevelopmental disorder with hypotonia and brain abnormalities
  • p.Thr438Ser No assertion criteria neurodevelopmental disorder with hypotonia and brain abnormalities

Conflicting classifications of pathogenicity 1

Benign 2

Likely benign 16

Uncertain significance 153