Sugi Variant

Sugi Variant/TMC1

TMC1 — 904 ClinVar variants

All ClinVar germline TMC1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 262 flagged for review →

91 Pathogenic · 21 Pathogenic/Likely pathogenic · 69 Likely pathogenic · 46 Conflicting · 53 Benign · 9 Benign/Likely benign · 344 Likely benign · 271 Uncertain significance

Full TMC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 262

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 18

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

Predictors lean, ClinVar uncertain 165

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification. · showing the 150 best-reviewed of 165

Predictors split 77

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

All TMC1 variants

Pathogenic 91

  • c.2130-1del Multiple submitters
  • c.236+1G>A Multiple submitters Monogenic hearing loss
  • c.236+1G>T Multiple submitters
  • c.884+1G>A Multiple submitters autosomal recessive nonsyndromic hearing loss 7
  • p.Arg264Ter Multiple submitters autosomal recessive nonsyndromic hearing loss 7
  • p.Arg34Ter Multiple submitters TMC1-related disorder
  • p.Arg389Ter Multiple submitters Rare genetic deafness
  • p.Arg512Ter Multiple submitters autosomal recessive nonsyndromic hearing loss 7
  • p.Arg604Ter Multiple submitters TMC1-related disorder
  • p.Gly197Arg Multiple submitters nonsyndromic genetic hearing loss ⚠
  • p.Met413fs Multiple submitters Rare genetic deafness
  • p.Trp588Ter Multiple submitters Inborn genetic diseases
  • c.1030-98_1177del Single submitter
  • c.1224+1G>T Single submitter
  • c.1224+2T>C Single submitter hearing loss, autosomal recessive
  • c.16+1G>A Single submitter
  • c.2125_2129+7del Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.236+2T>C Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.362+2T>C Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.453+1G>T Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.453+2T>G Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.535+1G>C Single submitter autosomal dominant nonsyndromic hearing loss 36
  • c.535+2dup Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.536-8T>A Single submitter TMC1-related disorder
  • c.(64+1_65-1 Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.64+2T>C Single submitter
  • c.65-4_77del Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.885-2A>C Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Ala237fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Ala594fs Single submitter
  • p.Ala712fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Arg362fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Arg445fs Single submitter
  • p.Arg74fs Single submitter Rare genetic deafness
  • p.Asn312fs Single submitter
  • p.Asn333fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Asn407fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Asn554fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Asn583Lys Single submitter autosomal recessive nonsyndromic hearing loss 7 ⚠
  • p.Asn671fs Single submitter
  • p.Asp302fs Single submitter
  • p.Gln395fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Glu122Ter Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Glu233fs Single submitter
  • p.Glu471Ter Single submitter
  • p.Glu570Ter Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Glu679Ter Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Glu82Ter Single submitter
  • p.Glu83Ter Single submitter
  • p.Glu95fs Single submitter
  • p.Gly267Glu Single submitter ⚠
  • p.Gly417Arg Single submitter
  • p.Gly417Glu Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Gly444Glu Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Ile84fs Single submitter nonsyndromic genetic hearing loss
  • p.Ile8fs Single submitter Rare genetic deafness
  • p.Leu205Pro Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Leu443_Gly444delinsTer Single submitter
  • p.Leu533fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Leu605Pro Single submitter TMC1-related disorder
  • p.Lys121fs Single submitter
  • p.Lys43fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Met283fs Single submitter Deafness
  • p.Met586fs Single submitter
  • p.Phe126fs Single submitter
  • p.Phe189fs Single submitter
  • p.Phe504fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Pro421Leu Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Ser223fs Single submitter
  • p.Ser288_Phe289delinsThrTer Single submitter
  • p.Ser2Ter Single submitter
  • p.Trp153Ter Single submitter
  • p.Trp170Ter Single submitter
  • p.Trp385Ter Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Trp557Ter Single submitter
  • p.Tyr323Ter Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Tyr381Ter Single submitter
  • p.Tyr455Ter Single submitter
  • p.Tyr563Ter Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Tyr565Ter Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Tyr715Ter Single submitter
  • p.Val6fs Single submitter autosomal dominant nonsyndromic hearing loss 36
  • c.1566+4A>G No assertion criteria autosomal recessive nonsyndromic hearing loss 7
  • c.16+1G>T No assertion criteria autosomal recessive nonsyndromic hearing loss 7
  • p.Arg77fs No assertion criteria autosomal recessive nonsyndromic hearing loss 7
  • p.Asp543Asn No assertion criteria autosomal dominant nonsyndromic hearing loss 36 ⚠
  • p.Glu740Ter No assertion criteria autosomal recessive nonsyndromic hearing loss 7
  • p.Ile177Thr No assertion criteria Moderate intellectual disability
  • p.Met418Lys No assertion criteria autosomal dominant nonsyndromic hearing loss 36
  • p.Pro511Leu No assertion criteria autosomal recessive nonsyndromic hearing loss 7
  • p.Val291fs No assertion criteria autosomal recessive nonsyndromic hearing loss 7

Pathogenic/Likely pathogenic 21

  • c.1763+3A>G Multiple submitters Rare genetic deafness
  • c.64+2T>A Multiple submitters autosomal recessive nonsyndromic hearing loss 7
  • c.741+1G>A Multiple submitters Rare genetic deafness
  • p.Ala351fs Multiple submitters TMC1-related disorder
  • p.Arg389Gln Multiple submitters nonsyndromic genetic hearing loss
  • p.Asn50fs Multiple submitters autosomal dominant nonsyndromic hearing loss 36
  • p.Asp572Asn Multiple submitters TMC1-related disorder ⚠
  • p.Asp572His Multiple submitters Monogenic hearing loss ⚠
  • p.Asp684His Multiple submitters TMC1-related disorder
  • p.Gln584Ter Multiple submitters autosomal recessive nonsyndromic hearing loss 7
  • p.Ile677Thr Multiple submitters autosomal dominant nonsyndromic hearing loss 36
  • p.Ser647Pro Multiple submitters Rare genetic deafness
  • p.Trp111Ter Multiple submitters TMC1-related disorder
  • p.Trp268Ter Multiple submitters
  • p.Trp559Ter Multiple submitters Rare genetic deafness
  • p.Tyr215Ter Multiple submitters TMC1-related disorder
  • p.Asn576Lys No assertion criteria Deafness ⚠
  • p.Cys420Tyr No assertion criteria hearing loss, autosomal recessive
  • p.Cys515Arg No assertion criteria hearing loss, autosomal recessive
  • p.Trp315Ter No assertion criteria hearing loss, autosomal recessive
  • p.Trp403Ter No assertion criteria hearing loss, autosomal recessive

Likely pathogenic 69

  • c.1405-2A>T Multiple submitters autosomal recessive nonsyndromic hearing loss 7
  • p.Asn467del Multiple submitters nonsyndromic genetic hearing loss
  • p.Ile266Thr Multiple submitters autosomal recessive nonsyndromic hearing loss 7 ⚠
  • p.Pro225Leu Multiple submitters Rare genetic deafness
  • c.1224+1G>A Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.1405-1G>C Single submitter
  • c.1567-1G>A Single submitter
  • c.1695+2T>G Single submitter
  • c.1763+1G>T Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.2003+1G>A Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.2004-10A>G Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.2208+1G>C Single submitter
  • c.2260+1G>T Single submitter TMC1-related disorder
  • c.362+1G>C Single submitter
  • c.453+2T>C Single submitter
  • c.453+5G>T Single submitter
  • c.535+1_535+3delinsAGT Single submitter
  • c.535+5G>A Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.536-1G>A Single submitter
  • c.536-1G>C Single submitter TMC1-related disorder
  • c.643-2A>G Single submitter autosomal dominant nonsyndromic hearing loss 36
  • c.742-1G>A Single submitter
  • c.742-1G>C Single submitter TMC1-related disorder
  • p.Ala250Thr Single submitter autosomal recessive nonsyndromic hearing loss 7 ⚠
  • p.Ala726fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Arg365Lys Single submitter hearing loss, autosomal recessive ⚠
  • p.Arg39Ter Single submitter autosomal dominant nonsyndromic hearing loss 36
  • p.Arg445Leu Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Arg71fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Asn199Ser Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Asn327Ile Single submitter TMC1-related disorder
  • p.Asn727fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Asp560fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Cys515Phe Single submitter
  • p.Gln584Arg Single submitter
  • p.Glu26fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Glu29fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Glu62Ter Single submitter TMC1-related disorder
  • p.Gly218Val Single submitter autosomal recessive nonsyndromic hearing loss 7 ⚠
  • p.Gly258Ser Single submitter autosomal recessive nonsyndromic hearing loss 7 ⚠
  • p.Gly267fs Single submitter
  • p.Gly267Val Single submitter
  • p.Gly305fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Gly78fs Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Ile103_Ala104delinsMetPro Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Lys125fs Single submitter TMC1-related disorder
  • p.Met113Val Single submitter TMC1-related disorder ⚠
  • p.Met418Thr Single submitter TMC1-related disorder ⚠
  • p.Phe189Leu Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Ser288Gly Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Ser379Asn Single submitter
  • p.Trp170fs Single submitter Deafness
  • p.Trp194Ter Single submitter TMC1-related disorder
  • p.Trp588Cys Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Tyr188Ter Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Tyr259Cys Single submitter nonsyndromic genetic hearing loss
  • p.Tyr287Ter Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Tyr433Cys Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Tyr433Ser Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Tyr433Ter Single submitter autosomal dominant nonsyndromic hearing loss 36
  • p.Val198fs Single submitter TMC1-related disorder
  • c.2003+2T>C No assertion criteria autosomal recessive nonsyndromic hearing loss 7
  • c.741+2dup No assertion criteria autosomal recessive nonsyndromic hearing loss 7
  • p.Glu679Lys No assertion criteria hearing loss, autosomal recessive ⚠
  • p.Gly585fs No assertion criteria hearing loss, autosomal recessive
  • p.Ser596Arg No assertion criteria hearing loss, autosomal recessive
  • p.Ser668Gly No assertion criteria autosomal recessive nonsyndromic hearing loss 7 ⚠
  • p.Tyr244Ter No assertion criteria autosomal recessive nonsyndromic hearing loss 7
  • p.Tyr455His No assertion criteria hearing loss, autosomal recessive

Conflicting classifications of pathogenicity 46

  • c.1029+7G>A Single submitter
  • c.1567-14T>G Single submitter autosomal dominant nonsyndromic hearing loss 36
  • c.237-5T>A Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.884+2dup Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.885-11T>C Single submitter
  • c.-124T>C Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.-275G>A Single submitter autosomal dominant nonsyndromic hearing loss 36
  • c.*106G>C Single submitter autosomal dominant nonsyndromic hearing loss 36
  • c.*156T>C Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.*183A>G Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.*26G>C Single submitter autosomal recessive nonsyndromic hearing loss 7
  • c.*28A>C Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Ala235Ser Single submitter autosomal recessive nonsyndromic hearing loss 7 ⚠
  • p.Ala690= Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Arg141Trp Single submitter autosomal recessive nonsyndromic hearing loss 7 ⚠
  • p.Arg445Cys Single submitter Rare genetic deafness ⚠
  • p.Arg445His Single submitter nonsyndromic genetic hearing loss ⚠
  • p.Arg759Cys Single submitter autosomal dominant nonsyndromic hearing loss 36 ⚠
  • p.Asn312Lys Single submitter ⚠
  • p.Asn357Ser Single submitter Inborn genetic diseases
  • p.Asp308Glu Single submitter Inborn genetic diseases ⚠
  • p.Asp47Glu Single submitter Inborn genetic diseases ⚠
  • p.Asp684Asn Single submitter autosomal dominant nonsyndromic hearing loss 36 ⚠
  • p.Glu118Ter Single submitter hearing loss disorder
  • p.Glu523= Single submitter
  • p.Gly135= Single submitter
  • p.Gly222Asp Single submitter autosomal dominant nonsyndromic hearing loss 36 ⚠
  • p.Leu209= Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Leu367Arg Single submitter TMC1-related disorder ⚠
  • p.Leu711= Single submitter
  • p.Met411Ile Single submitter ⚠
  • p.Met654Val Single submitter nonsyndromic genetic hearing loss ⚠
  • p.Pro274Leu Single submitter hearing loss disorder ⚠
  • p.Pro421= Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Pro511His Single submitter TMC1-related disorder ⚠
  • p.Pro566Ala Single submitter ⚠
  • p.Ser668Arg Single submitter sensorineural hearing loss disorder ⚠
  • p.Thr265= Single submitter autosomal dominant nonsyndromic hearing loss 36
  • p.Thr528= Single submitter autosomal dominant nonsyndromic hearing loss 36
  • p.Tyr323Cys Single submitter Inborn genetic diseases ⚠
  • p.Tyr381Asn Single submitter Rare genetic deafness ⚠
  • p.Tyr536= Single submitter autosomal recessive nonsyndromic hearing loss 7
  • p.Val254Ile Single submitter autosomal dominant nonsyndromic hearing loss 36 ⚠
  • p.Val372Met Single submitter TMC1-related disorder ⚠
  • p.Val537Ile Single submitter autosomal recessive nonsyndromic hearing loss 7 ⚠
  • p.Val676Asp Single submitter autosomal dominant nonsyndromic hearing loss 36 ⚠

Benign 53

Benign/Likely benign 9

Likely benign 344

Showing the top 300 by review status; the full set is in the sitemap.

Uncertain significance 271