TMC8 — 572 ClinVar variants

All ClinVar germline TMC8 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 231 flagged for review →

20 Pathogenic · 1 Pathogenic/Likely pathogenic · 8 Likely pathogenic · 14 Conflicting · 39 Benign · 13 Benign/Likely benign · 228 Likely benign · 249 Uncertain significance

Full TMC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 231

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 agree, ClinVar conflicts 10

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

Predictors lean, ClinVar uncertain 180

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 180

Predictors split 41

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

All TMC8 variants

Pathogenic 20

  • p.Arg190Ter Multiple submitters epidermodysplasia verruciformis
  • p.Arg295fs Multiple submitters epidermodysplasia verruciformis, susceptibility to, 2
  • p.Ala188fs Single submitter epidermodysplasia verruciformis
  • p.Asp142fs Single submitter epidermodysplasia verruciformis
  • p.Asp251fs Single submitter epidermodysplasia verruciformis
  • p.Gln236fs Single submitter epidermodysplasia verruciformis
  • p.Gln291fs Single submitter epidermodysplasia verruciformis
  • p.Glu330Ter Single submitter epidermodysplasia verruciformis
  • p.Glu362Ter Single submitter epidermodysplasia verruciformis
  • p.Glu425fs Single submitter epidermodysplasia verruciformis
  • p.Glu577Ter Single submitter epidermodysplasia verruciformis
  • p.Gly342fs Single submitter epidermodysplasia verruciformis
  • p.Leu221fs Single submitter epidermodysplasia verruciformis
  • p.Leu233fs Single submitter epidermodysplasia verruciformis
  • p.Leu300fs Single submitter epidermodysplasia verruciformis
  • p.Leu583fs Single submitter epidermodysplasia verruciformis
  • p.Lys403fs Single submitter epidermodysplasia verruciformis
  • p.Ser422fs Single submitter epidermodysplasia verruciformis
  • p.Val304fs Single submitter epidermodysplasia verruciformis, susceptibility to, 2
  • p.Val343fs Single submitter epidermodysplasia verruciformis

Pathogenic/Likely pathogenic 1

  • c.1824-1G>C Multiple submitters epidermodysplasia verruciformis

Likely pathogenic 8

  • c.449-1G>T Multiple submitters TMC8-related disorder
  • c.1128-2A>G Single submitter epidermodysplasia verruciformis
  • c.1534-1G>C Single submitter epidermodysplasia verruciformis
  • c.1664+1G>A Single submitter epidermodysplasia verruciformis
  • c.668+1G>A Single submitter epidermodysplasia verruciformis
  • c.669-2A>C Single submitter epidermodysplasia verruciformis
  • c.987+1G>A Single submitter epidermodysplasia verruciformis
  • c.987+2T>A Single submitter epidermodysplasia verruciformis

Conflicting classifications of pathogenicity 14

Benign 39

Benign/Likely benign 13

  • c.1350-14T>G Multiple submitters epidermodysplasia verruciformis
  • c.1350-16C>G Multiple submitters epidermodysplasia verruciformis
  • c.1665-19C>T Multiple submitters epidermodysplasia verruciformis
  • c.988-4G>A Multiple submitters epidermodysplasia verruciformis
  • c.*5T>G Multiple submitters epidermodysplasia verruciformis, susceptibility to, 2
  • p.Arg222Trp Multiple submitters epidermodysplasia verruciformis
  • p.Arg223Gln Multiple submitters epidermodysplasia verruciformis
  • p.Asn306= Multiple submitters epidermodysplasia verruciformis
  • p.Asn306Ile Multiple submitters epidermodysplasia verruciformis
  • p.Gly93= Multiple submitters epidermodysplasia verruciformis
  • p.Leu543= Multiple submitters epidermodysplasia verruciformis
  • p.Pro160= Multiple submitters epidermodysplasia verruciformis
  • p.Pro524Leu Multiple submitters epidermodysplasia verruciformis

Likely benign 228

  • c.1127+18dup Multiple submitters epidermodysplasia verruciformis
  • c.1128-12C>G Multiple submitters epidermodysplasia verruciformis
  • c.1251+134C>G Multiple submitters
  • c.1251+14C>T Multiple submitters epidermodysplasia verruciformis
  • c.1251+169G>A Multiple submitters
  • c.1251+20G>C Multiple submitters epidermodysplasia verruciformis
  • c.1350-17C>T Multiple submitters epidermodysplasia verruciformis
  • c.1534-9C>T Multiple submitters epidermodysplasia verruciformis
  • c.298+10G>C Multiple submitters epidermodysplasia verruciformis
  • c.449-11C>T Multiple submitters epidermodysplasia verruciformis
  • c.531+19G>A Multiple submitters epidermodysplasia verruciformis
  • c.532-18C>G Multiple submitters epidermodysplasia verruciformis
  • c.668+14C>T Multiple submitters epidermodysplasia verruciformis
  • c.669-5C>T Multiple submitters epidermodysplasia verruciformis
  • c.816+10C>T Multiple submitters epidermodysplasia verruciformis
  • c.987+14G>A Multiple submitters epidermodysplasia verruciformis
  • p.Ala480= Multiple submitters epidermodysplasia verruciformis
  • p.Glu468= Multiple submitters epidermodysplasia verruciformis
  • p.Ile478= Multiple submitters epidermodysplasia verruciformis
  • p.Leu296= Multiple submitters epidermodysplasia verruciformis
  • p.Pro193= Multiple submitters epidermodysplasia verruciformis
  • p.Pro576= Multiple submitters Inborn genetic diseases
  • p.Ser243= Multiple submitters epidermodysplasia verruciformis
  • p.Ser389= Multiple submitters epidermodysplasia verruciformis
  • p.Ser422= Multiple submitters epidermodysplasia verruciformis
  • p.Thr150= Multiple submitters epidermodysplasia verruciformis
  • p.Thr220= Multiple submitters epidermodysplasia verruciformis
  • p.Thr292= Multiple submitters epidermodysplasia verruciformis
  • p.Tyr186= Multiple submitters epidermodysplasia verruciformis
  • p.Val575= Multiple submitters epidermodysplasia verruciformis
  • c.1127+11C>T Single submitter epidermodysplasia verruciformis
  • c.1127+16G>C Single submitter epidermodysplasia verruciformis
  • c.1128-8G>T Single submitter epidermodysplasia verruciformis
  • c.1251+12C>T Single submitter epidermodysplasia verruciformis
  • c.1251+13C>G Single submitter epidermodysplasia verruciformis
  • c.1251+15G>A Single submitter epidermodysplasia verruciformis
  • c.1251+16G>A Single submitter epidermodysplasia verruciformis
  • c.1251+17C>T Single submitter epidermodysplasia verruciformis
  • c.1251+18G>A Single submitter epidermodysplasia verruciformis
  • c.1251+7G>A Single submitter
  • c.1251+8G>A Single submitter epidermodysplasia verruciformis
  • c.1252-10T>G Single submitter epidermodysplasia verruciformis
  • c.1252-11C>A Single submitter epidermodysplasia verruciformis
  • c.1252-14C>A Single submitter epidermodysplasia verruciformis
  • c.1252-5C>G Single submitter epidermodysplasia verruciformis
  • c.1252-8C>T Single submitter epidermodysplasia verruciformis
  • c.1349+10G>A Single submitter epidermodysplasia verruciformis
  • c.1349+11G>C Single submitter epidermodysplasia verruciformis
  • c.1349+13G>T Single submitter epidermodysplasia verruciformis
  • c.1349+18A>T Single submitter epidermodysplasia verruciformis
  • c.1349+19C>T Single submitter
  • c.1349+8C>T Single submitter epidermodysplasia verruciformis
  • c.1349+9C>T Single submitter epidermodysplasia verruciformis
  • c.1350-18A>T Single submitter epidermodysplasia verruciformis
  • c.1534-14G>A Single submitter epidermodysplasia verruciformis
  • c.1534-15T>C Single submitter epidermodysplasia verruciformis
  • c.1534-16T>C Single submitter epidermodysplasia verruciformis
  • c.1534-19C>T Single submitter epidermodysplasia verruciformis
  • c.1664+10A>G Single submitter
  • c.1664+13G>A Single submitter epidermodysplasia verruciformis
  • c.1664+15_1664+17del Single submitter epidermodysplasia verruciformis
  • c.1664+15A>G Single submitter epidermodysplasia verruciformis
  • c.1664+21dup Single submitter
  • c.1665-19C>A Single submitter epidermodysplasia verruciformis
  • c.1665-6C>T Single submitter epidermodysplasia verruciformis
  • c.1823+15C>T Single submitter epidermodysplasia verruciformis
  • c.1823+16G>A Single submitter epidermodysplasia verruciformis
  • c.1823+17G>A Single submitter epidermodysplasia verruciformis
  • c.1823+20C>A Single submitter epidermodysplasia verruciformis
  • c.1823+7A>G Single submitter epidermodysplasia verruciformis
  • c.1824-13C>T Single submitter epidermodysplasia verruciformis
  • c.1824-14C>T Single submitter epidermodysplasia verruciformis
  • c.1824-20G>A Single submitter epidermodysplasia verruciformis
  • c.1902+10C>T Single submitter epidermodysplasia verruciformis
  • c.1902+12C>T Single submitter epidermodysplasia verruciformis
  • c.1902+13G>A Single submitter epidermodysplasia verruciformis
  • c.1902+13G>T Single submitter epidermodysplasia verruciformis
  • c.1902+15G>A Single submitter epidermodysplasia verruciformis
  • c.1902+20G>C Single submitter
  • c.1902+9C>G Single submitter epidermodysplasia verruciformis
  • c.1903-13G>A Single submitter epidermodysplasia verruciformis
  • c.1903-17A>G Single submitter
  • c.1903-7_1903-5del Single submitter epidermodysplasia verruciformis
  • c.1903-8C>T Single submitter epidermodysplasia verruciformis
  • c.298+13C>A Single submitter epidermodysplasia verruciformis
  • c.298+16C>T Single submitter epidermodysplasia verruciformis
  • c.298+8C>A Single submitter epidermodysplasia verruciformis
  • c.448+10A>C Single submitter epidermodysplasia verruciformis
  • c.448+12G>A Single submitter epidermodysplasia verruciformis
  • c.448+17C>G Single submitter epidermodysplasia verruciformis
  • c.448+19A>G Single submitter epidermodysplasia verruciformis
  • c.448+7G>T Single submitter epidermodysplasia verruciformis
  • c.448+9_448+15del Single submitter epidermodysplasia verruciformis
  • c.449-15del Single submitter
  • c.449-18C>T Single submitter
  • c.449-19C>A Single submitter epidermodysplasia verruciformis
  • c.449-8C>T Single submitter epidermodysplasia verruciformis
  • c.531+20G>C Single submitter epidermodysplasia verruciformis
  • c.531+7G>A Single submitter epidermodysplasia verruciformis
  • c.532-10C>T Single submitter epidermodysplasia verruciformis
  • c.532-11G>A Single submitter
  • c.532-12C>G Single submitter epidermodysplasia verruciformis
  • c.532-12C>T Single submitter epidermodysplasia verruciformis
  • c.532-14G>A Single submitter epidermodysplasia verruciformis
  • c.532-15C>T Single submitter epidermodysplasia verruciformis
  • c.532-43C>G Single submitter
  • c.532-4C>A Single submitter epidermodysplasia verruciformis
  • c.532-6C>T Single submitter epidermodysplasia verruciformis
  • c.668+8C>G Single submitter epidermodysplasia verruciformis
  • c.668+8C>T Single submitter epidermodysplasia verruciformis
  • c.668+9G>A Single submitter epidermodysplasia verruciformis
  • c.669-129C>T Single submitter
  • c.669-17G>A Single submitter epidermodysplasia verruciformis
  • c.669-18T>C Single submitter epidermodysplasia verruciformis
  • c.669-4G>A Single submitter epidermodysplasia verruciformis
  • c.669-4G>T Single submitter epidermodysplasia verruciformis
  • c.816+15G>C Single submitter epidermodysplasia verruciformis
  • c.816+16_816+19del Single submitter epidermodysplasia verruciformis
  • c.817-12C>T Single submitter
  • c.817-18C>A Single submitter epidermodysplasia verruciformis
  • c.817-6G>C Single submitter epidermodysplasia verruciformis
  • c.987+16A>G Single submitter epidermodysplasia verruciformis
  • c.987+20A>T Single submitter epidermodysplasia verruciformis
  • c.987+7G>T Single submitter epidermodysplasia verruciformis
  • c.987+8G>T Single submitter epidermodysplasia verruciformis
  • c.988-5C>T Single submitter epidermodysplasia verruciformis
  • c.988-7C>G Single submitter epidermodysplasia verruciformis
  • p.Ala188= Single submitter epidermodysplasia verruciformis
  • p.Ala240= Single submitter epidermodysplasia verruciformis
  • p.Ala260= Single submitter epidermodysplasia verruciformis
  • p.Ala290= Single submitter epidermodysplasia verruciformis
  • p.Ala316= Single submitter epidermodysplasia verruciformis
  • p.Ala383= Single submitter epidermodysplasia verruciformis
  • p.Ala520= Single submitter epidermodysplasia verruciformis
  • p.Ala598= Single submitter epidermodysplasia verruciformis
  • p.Ala698= Single submitter epidermodysplasia verruciformis
  • p.Ala85= Single submitter epidermodysplasia verruciformis
  • p.Arg466= Single submitter epidermodysplasia verruciformis
  • p.Arg523= Single submitter epidermodysplasia verruciformis
  • p.Arg670= Single submitter epidermodysplasia verruciformis
  • p.Asn148= Single submitter epidermodysplasia verruciformis
  • p.Asn269= Single submitter epidermodysplasia verruciformis
  • p.Asn303= Single submitter epidermodysplasia verruciformis
  • p.Asn371= Single submitter epidermodysplasia verruciformis
  • p.Asn412= Single submitter epidermodysplasia verruciformis
  • p.Cys414= Single submitter epidermodysplasia verruciformis
  • p.Cys675= Single submitter epidermodysplasia verruciformis
  • p.Gln325= Single submitter epidermodysplasia verruciformis
  • p.Gln482= Single submitter epidermodysplasia verruciformis
  • p.Glu276= Single submitter epidermodysplasia verruciformis
  • p.Glu426= Single submitter epidermodysplasia verruciformis
  • p.Glu725= Single submitter epidermodysplasia verruciformis
  • p.Glu97= Single submitter epidermodysplasia verruciformis
  • p.Gly162= Single submitter epidermodysplasia verruciformis
  • p.Gly219= Single submitter epidermodysplasia verruciformis
  • p.Gly227= Single submitter epidermodysplasia verruciformis
  • p.Gly654= Single submitter epidermodysplasia verruciformis
  • p.His597= Single submitter epidermodysplasia verruciformis
  • p.His686Pro Single submitter Inborn genetic diseases
  • p.Ile201= Single submitter epidermodysplasia verruciformis
  • p.Ile254= Single submitter
  • p.Ile317= Single submitter epidermodysplasia verruciformis
  • p.Ile344= Single submitter epidermodysplasia verruciformis
  • p.Leu184= Single submitter epidermodysplasia verruciformis
  • p.Leu214= Single submitter epidermodysplasia verruciformis
  • p.Leu234= Single submitter epidermodysplasia verruciformis
  • p.Leu275= Single submitter epidermodysplasia verruciformis
  • p.Leu297= Single submitter epidermodysplasia verruciformis
  • p.Leu305= Single submitter epidermodysplasia verruciformis
  • p.Leu339= Single submitter epidermodysplasia verruciformis
  • p.Leu353= Single submitter epidermodysplasia verruciformis
  • p.Leu385= Single submitter epidermodysplasia verruciformis
  • p.Leu397= Single submitter epidermodysplasia verruciformis
  • p.Leu437= Single submitter epidermodysplasia verruciformis
  • p.Leu470= Single submitter epidermodysplasia verruciformis
  • p.Leu476= Single submitter epidermodysplasia verruciformis
  • p.Leu489= Single submitter epidermodysplasia verruciformis
  • p.Leu536= Single submitter epidermodysplasia verruciformis
  • p.Leu540= Single submitter epidermodysplasia verruciformis
  • p.Leu578= Single submitter epidermodysplasia verruciformis
  • p.Leu642= Single submitter epidermodysplasia verruciformis
  • p.Leu88= Single submitter epidermodysplasia verruciformis
  • p.Leu95= Single submitter epidermodysplasia verruciformis
  • p.Lys662= Single submitter epidermodysplasia verruciformis
  • p.Phe441= Single submitter epidermodysplasia verruciformis
  • p.Phe601= Single submitter epidermodysplasia verruciformis
  • p.Pro209= Single submitter epidermodysplasia verruciformis
  • p.Pro229= Single submitter epidermodysplasia verruciformis
  • p.Pro340= Single submitter epidermodysplasia verruciformis
  • p.Pro352= Single submitter epidermodysplasia verruciformis
  • p.Pro524Arg Single submitter Inborn genetic diseases ⚠
  • p.Pro584= Single submitter epidermodysplasia verruciformis
  • p.Pro659= Single submitter epidermodysplasia verruciformis
  • p.Pro671= Single submitter epidermodysplasia verruciformis
  • p.Pro681= Single submitter epidermodysplasia verruciformis
  • p.Pro684= Single submitter epidermodysplasia verruciformis
  • p.Pro691= Single submitter epidermodysplasia verruciformis
  • p.Pro721= Single submitter epidermodysplasia verruciformis
  • p.Ser196= Single submitter epidermodysplasia verruciformis
  • p.Ser197= Single submitter epidermodysplasia verruciformis
  • p.Ser298= Single submitter
  • p.Ser522= Single submitter epidermodysplasia verruciformis
  • p.Ser600= Single submitter epidermodysplasia verruciformis
  • p.Ser647= Single submitter epidermodysplasia verruciformis
  • p.Ser656Asn Single submitter epidermodysplasia verruciformis
  • p.Ser673= Single submitter epidermodysplasia verruciformis
  • p.Ser722= Single submitter epidermodysplasia verruciformis
  • p.Thr288= Single submitter epidermodysplasia verruciformis
  • p.Thr321= Single submitter epidermodysplasia verruciformis
  • p.Thr368= Single submitter epidermodysplasia verruciformis
  • p.Thr438= Single submitter epidermodysplasia verruciformis
  • p.Thr483= Single submitter epidermodysplasia verruciformis
  • p.Thr612= Single submitter epidermodysplasia verruciformis
  • p.Tyr199= Single submitter epidermodysplasia verruciformis
  • p.Tyr338= Single submitter epidermodysplasia verruciformis
  • p.Tyr409= Single submitter epidermodysplasia verruciformis
  • p.Tyr551= Single submitter epidermodysplasia verruciformis
  • p.Tyr663= Single submitter epidermodysplasia verruciformis
  • p.Tyr96= Single submitter epidermodysplasia verruciformis
  • p.Val198= Single submitter epidermodysplasia verruciformis
  • p.Val256= Single submitter epidermodysplasia verruciformis
  • p.Val304Ile Single submitter Inborn genetic diseases
  • p.Val343= Single submitter epidermodysplasia verruciformis
  • p.Val390= Single submitter epidermodysplasia verruciformis
  • p.Val423= Single submitter epidermodysplasia verruciformis
  • p.Val547= Single submitter epidermodysplasia verruciformis
  • p.Val695= Single submitter epidermodysplasia verruciformis
  • c.*7C>A No assertion criteria TMC8-related disorder

Uncertain significance 249