Sugi Variant

Sugi Variant/SIX1

SIX1 — 287 ClinVar variants

All ClinVar germline SIX1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 127 flagged for review →

8 Pathogenic · 4 Pathogenic/Likely pathogenic · 20 Likely pathogenic · 20 Conflicting · 9 Benign · 13 Benign/Likely benign · 52 Likely benign · 161 Uncertain significance

Full SIX1 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 1

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

Predictors agree, ClinVar conflicts 9

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 15

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

All SIX1 variants

Pathogenic 8

  • p.Arg110Trp Multiple submitters autosomal dominant nonsyndromic hearing loss 23
  • p.Tyr129Cys Multiple submitters SIX1-related disorder
  • p.Arg113Ter Single submitter autosomal dominant nonsyndromic hearing loss 23
  • p.Glu19fs Single submitter branchiootic syndrome 3
  • p.Leu103fs Single submitter branchiootic syndrome 3
  • p.Lys114Glu Single submitter branchiootic syndrome 3
  • p.Ser76Ter Single submitter Inborn genetic diseases
  • p.Trp122Arg No assertion criteria branchiootic syndrome 3

Pathogenic/Likely pathogenic 4

  • p.Asn174Lys Multiple submitters branchiootic syndrome 2
  • p.Arg110Gln Multiple submitters branchiootic syndrome 3
  • p.Glu125Lys Multiple submitters SIX1-related disorder
  • p.Glu133del Multiple submitters SIX1-related disorder

Likely pathogenic 20

  • p.Val106Met Multiple submitters branchiootic syndrome 3
  • p.Arg110Leu Single submitter autosomal dominant nonsyndromic hearing loss 23
  • p.Arg178Ser Single submitter Inborn genetic diseases
  • p.Asn245Asp Single submitter branchiootic syndrome 3 ⚠
  • p.Cys16Phe Single submitter SIX1-related disorder
  • p.Gln167Arg Single submitter branchio-oto-renal syndrome
  • p.Glu141Ter Single submitter branchiootic syndrome 3
  • p.Gly107fs Single submitter autosomal dominant nonsyndromic hearing loss 23
  • p.Leu139Arg Single submitter branchiootic syndrome 3
  • p.Lys173Asn Single submitter
  • p.Pro118Leu Single submitter autosomal dominant nonsyndromic hearing loss 23
  • p.Trp122Ter Single submitter branchiootic syndrome 3
  • p.Trp171Ter Single submitter Monogenic hearing loss
  • p.Tyr129_Cys130del Single submitter branchiootic syndrome 3
  • p.Tyr129His Single submitter branchiootic syndrome 3 ⚠
  • p.Val106Glu Single submitter SIX1-related disorder
  • p.Val106Leu Single submitter autosomal dominant nonsyndromic hearing loss
  • c.560+1G>C No assertion criteria branchiootic syndrome 3
  • p.Arg101fs No assertion criteria SIX1-related disorder
  • p.Lys154Ter No assertion criteria branchiootic syndrome 3

Conflicting classifications of pathogenicity 20

Benign 9

Benign/Likely benign 13

  • c.561-34_561-31del Multiple submitters branchiootic syndrome 3
  • c.-137C>T Multiple submitters branchiootic syndrome 3
  • c.*297T>G Multiple submitters branchiootic syndrome 3
  • p.Ala54= Multiple submitters branchiootorenal syndrome 1
  • p.Arg60= Multiple submitters branchiootic syndrome 3
  • p.Pro205= Multiple submitters branchiootorenal syndrome 1
  • p.Pro249Gln Multiple submitters branchiootic syndrome 3
  • c.-14G>T Single submitter autosomal dominant nonsyndromic hearing loss 23
  • c.-184A>C Single submitter branchiootic syndrome 3
  • c.-24C>T Single submitter branchiootic syndrome 3
  • c.*1044G>T Single submitter branchiootic syndrome 3
  • c.*1079T>A Single submitter branchiootic syndrome 3
  • c.*443A>G Single submitter branchiootic syndrome 3

Likely benign 52

  • c.560+7G>C Multiple submitters autosomal dominant nonsyndromic hearing loss 23
  • c.561-13C>T Multiple submitters autosomal dominant nonsyndromic hearing loss 23
  • p.Ala158= Multiple submitters autosomal dominant nonsyndromic hearing loss 23
  • p.Arg155= Multiple submitters branchiootic syndrome 3
  • p.Gln235His Multiple submitters autosomal dominant nonsyndromic hearing loss 23
  • p.His240= Multiple submitters branchiootic syndrome 3
  • p.Leu272= Multiple submitters branchiootic syndrome 3
  • p.Pro38= Multiple submitters
  • c.560+174G>C Single submitter
  • c.560+25C>G Single submitter
  • c.561-10dup Single submitter autosomal dominant nonsyndromic hearing loss 23
  • c.561-14C>T Single submitter autosomal dominant nonsyndromic hearing loss 23
  • c.561-19G>A Single submitter branchiootic syndrome 3
  • c.561-21G>A Single submitter
  • c.-13G>C Single submitter
  • c.-45C>T Single submitter
  • c.*264_*265del Single submitter
  • c.*767A>T Single submitter branchiootic syndrome 3
  • p.Ala181= Single submitter branchiootic syndrome 3
  • p.Ala241Thr Single submitter
  • p.Ala52= Single submitter autosomal dominant nonsyndromic hearing loss 23
  • p.Arg113= Single submitter
  • p.Arg119= Single submitter branchiootic syndrome 3
  • p.Asn46= Single submitter branchiootic syndrome 3
  • p.Asp227= Single submitter branchiootic syndrome 3
  • p.Gln235= Single submitter
  • p.Glu71= Single submitter
  • p.Gly283= Single submitter branchiootic syndrome 3
  • p.Gly8= Single submitter branchiootic syndrome 3
  • p.Ile69= Single submitter
  • p.Leu203= Single submitter branchiootic syndrome 3
  • p.Leu232= Single submitter autosomal dominant nonsyndromic hearing loss 23
  • p.Leu271= Single submitter branchiootic syndrome 3
  • p.Leu30= Single submitter
  • p.Leu37= Single submitter
  • p.Leu86= Single submitter
  • p.Lys89= Single submitter autosomal dominant nonsyndromic hearing loss 23
  • p.Phe75= Single submitter autosomal dominant nonsyndromic hearing loss 23
  • p.Pro149= Single submitter autosomal dominant nonsyndromic hearing loss 23
  • p.Ser284= Single submitter branchiootic syndrome 3
  • p.Ser48= Single submitter
  • p.Ser76= Single submitter autosomal dominant nonsyndromic hearing loss 23
  • p.Ter285= Single submitter branchiootic syndrome 3
  • p.Thr120= Single submitter
  • p.Thr161= Single submitter branchiootic syndrome 3
  • p.Thr166= Single submitter branchiootic syndrome 3
  • p.Thr190= Single submitter branchiootic syndrome 3
  • p.Thr252= Single submitter
  • p.Thr262= Single submitter autosomal dominant nonsyndromic hearing loss 23
  • p.Val138= Single submitter branchiootic syndrome 3
  • p.Val17= Single submitter autosomal dominant nonsyndromic hearing loss 23
  • p.Val49= Single submitter

Uncertain significance 161