Sugi Variant

Sugi Variant/HSPB8

HSPB8 — 271 ClinVar variants

All ClinVar germline HSPB8 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 128 flagged for review →

8 Pathogenic · 2 Pathogenic/Likely pathogenic · 5 Likely pathogenic · 7 Conflicting · 22 Benign · 8 Benign/Likely benign · 59 Likely benign · 160 Uncertain significance

Full HSPB8 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 128

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 4

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

Predictors lean, ClinVar uncertain 94

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

Predictors split 30

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

All HSPB8 variants

Pathogenic 8

  • p.Lys141Glu Multiple submitters HSPB8-related disorder
  • p.Gln191fs Single submitter myopathy, myofibrillar, 13, with rimmed vacuoles
  • p.Lys141Met Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Ser180fs Single submitter myopathy, myofibrillar, 13, with rimmed vacuoles
  • p.Glu192fs No assertion criteria myopathy, myofibrillar, 13, with rimmed vacuoles
  • p.Lys141Asn No assertion criteria neuronopathy, distal hereditary motor, type 2A
  • p.Thr176fs No assertion criteria myopathy, myofibrillar, 13, with rimmed vacuoles
  • p.Thr194fs No assertion criteria myopathy, myofibrillar, 13, with rimmed vacuoles

Pathogenic/Likely pathogenic 2

  • p.Gln170fs Multiple submitters myopathy, autophagic vacuolar, infantile-onset
  • p.Gln188fs Multiple submitters neuronopathy, distal hereditary motor, type 2A

Likely pathogenic 5

Conflicting classifications of pathogenicity 7

Benign 22

  • c.368-106T>C Multiple submitters
  • c.431+83C>T Multiple submitters
  • c.432-134G>A Multiple submitters
  • c.-193T>C Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • c.*644A>G Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • c.*684G>A Multiple submitters neuronopathy, distal hereditary motor, type 2A
  • p.Asn184= Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • p.Glu179Gln Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • p.Ile134= Multiple submitters neuronopathy, distal hereditary motor, type 2A
  • p.Thr194= Multiple submitters neuronopathy, distal hereditary motor, type 2A
  • c.367+93G>T Single submitter
  • c.431+155A>G Single submitter
  • c.431+220C>T Single submitter
  • c.-457A>G Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.*440C>G Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.*581G>A Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.*616C>G Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.*616C>T Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.*848TAA[10] Single submitter
  • c.*848TAA[6] Single submitter
  • c.*848TAA[7] Single submitter
  • p.Ser57= Single submitter Charcot-Marie-Tooth disease axonal type 2L

Benign/Likely benign 8

  • c.432-15G>A Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • c.432-16C>T Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • c.*848TAA[9] Multiple submitters intellectual disability, autosomal dominant 46
  • p.Arg78Met Multiple submitters Inborn genetic diseases
  • p.Glu167Lys Multiple submitters Inborn genetic diseases ⚠
  • p.Leu16= Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • p.Pro49= Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • p.Pro89Arg Multiple submitters Inborn genetic diseases

Likely benign 59

  • c.432-139G>A Multiple submitters
  • p.Arg65= Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • p.Glu185Lys Multiple submitters Inborn genetic diseases
  • p.Gly178= Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • p.His125= Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • p.Ser66= Multiple submitters Inborn genetic diseases
  • p.Tyr118= Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • c.367+10G>A Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.367+10G>T Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.367+12G>C Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.367+18G>A Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.367+20G>A Single submitter
  • c.367+305G>A Single submitter
  • c.431+14A>C Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.431+14A>T Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.431+15G>A Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.431+19T>C Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.431+8A>G Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.431+9C>T Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.432-10T>C Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.432-196A>G Single submitter
  • c.432-8T>C Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.-35T>A Single submitter
  • c.*19T>A Single submitter
  • p.Ala156= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Ala83= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Arg15= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Arg17= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Arg29= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Asn183= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Asp42= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Glu120= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Glu161= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Glu167= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Gly117= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Gly67= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Gly85= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.His103= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Ile166= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Leu110= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Leu164= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Leu30= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Leu31= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Lys124= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Phe91= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Pro13= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Pro7= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Pro70= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Pro88= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Ser104= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Ser27= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Ser58= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Thr45= Single submitter
  • p.Thr76= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Val119= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Val81= Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Val81Leu Single submitter
  • c.*881C>T No assertion criteria HSPB8-related disorder
  • p.Cys99= No assertion criteria HSPB8-related disorder

Uncertain significance 160

  • c.-172G>C Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • c.-201G>T Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • c.*123G>A Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • p.Ala46Asp Multiple submitters Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Ala77Thr Multiple submitters Inborn genetic diseases ⚠
  • p.Arg17His Multiple submitters Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Arg29Cys Multiple submitters Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Arg29Ser Multiple submitters Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Arg55His Multiple submitters Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Asp32Ala Multiple submitters Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Asp50Asn Multiple submitters Inborn genetic diseases ⚠
  • p.Asp50Val Multiple submitters Inborn genetic diseases
  • p.Cys195Tyr Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • p.Gln144Glu Multiple submitters Inborn genetic diseases ⚠
  • p.Glu94Lys Multiple submitters Inborn genetic diseases
  • p.Gly67Val Multiple submitters Inborn genetic diseases ⚠
  • p.Leu186Phe Multiple submitters Inborn genetic diseases ⚠
  • p.Phe177Ser Multiple submitters Inborn genetic diseases ⚠
  • p.Pro107Ser Multiple submitters Inborn genetic diseases ⚠
  • p.Pro160Leu Multiple submitters Inborn genetic diseases ⚠
  • p.Pro172fs Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • p.Pro39Leu Multiple submitters Inborn genetic diseases ⚠
  • p.Pro70Ser Multiple submitters Inborn genetic diseases ⚠
  • p.Pro90fs Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • p.Pro90Leu Multiple submitters neuronopathy, distal hereditary motor, type 2A ⚠
  • p.Ser175Ala Multiple submitters Inborn genetic diseases ⚠
  • p.Ser190Arg Multiple submitters Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Ser47Cys Multiple submitters Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Trp48Ter Multiple submitters Charcot-Marie-Tooth disease axonal type 2L
  • p.Val171Ala Multiple submitters Inborn genetic diseases ⚠
  • c.367+57del Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.367+6T>C Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.367+8_367+31dup Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.-314T>C Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.-419A>T Single submitter neuronopathy, distal hereditary motor, type 2A
  • c.-480C>G Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.-489G>A Single submitter neuronopathy, distal hereditary motor, type 2A
  • c.-522C>G Single submitter neuronopathy, distal hereditary motor, type 2A
  • c.*330A>T Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.*504T>C Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.*648A>G Single submitter neuronopathy, distal hereditary motor, type 2A
  • c.*67T>G Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.*788C>T Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • c.*803T>C Single submitter neuronopathy, distal hereditary motor, type 2A
  • c.*860T>C Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Ala147Thr Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Ala168Thr Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Ala46= Single submitter
  • p.Ala46Thr Single submitter Inborn genetic diseases ⚠
  • p.Ala52Asp Single submitter ⚠
  • p.Ala59Thr Single submitter ⚠
  • p.Ala77Ser Single submitter ⚠
  • p.Arg15Cys Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Arg15His Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Arg17Cys Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Arg17Leu Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Arg17Pro Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Arg18Gly Single submitter ⚠
  • p.Arg18Ter Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Arg22Gln Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Arg29His Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Arg65Lys Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Arg71Gln Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Arg71Trp Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Arg86Lys Single submitter ⚠
  • p.Asn138Asp Single submitter ⚠
  • p.Asp189fs Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Asp32Gly Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Asp32Val Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Asp38Gly Single submitter ⚠
  • p.Asp3Glu Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Asp42Gly Single submitter ⚠
  • p.Asp43Asn Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Asp43His Single submitter ⚠
  • p.Asp50Glu Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Cys10Gly Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Gln129Pro Single submitter Inborn genetic diseases ⚠
  • p.Gln129Ter Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Gln130Glu Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Gln170Arg Single submitter Inborn genetic diseases ⚠
  • p.Gln170His Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Gln170Lys Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Gln170Pro Single submitter Inborn genetic diseases ⚠
  • p.Glu126fs Single submitter
  • p.Glu131Lys Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Glu179Gly Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Glu84Lys Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Glu94Gly Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Gly117Arg Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Gly133Ser Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Gly4Arg Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Gly4Asp Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Gly4Ser Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Gly62Asp Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Gly62fs Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Gly72Asp Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Gly72fs Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Gly80Ala Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Gly93Glu Single submitter ⚠
  • p.His11Arg Single submitter ⚠
  • p.His11Pro Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.His125Arg Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Leu158Phe Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Leu163Val Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Leu16Arg Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Leu31Met Single submitter ⚠
  • p.Leu53Val Single submitter Inborn genetic diseases ⚠
  • p.Leu56Ile Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Leu64Val Single submitter Inborn genetic diseases ⚠
  • p.Lys106Arg Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Lys141Gln Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Met111_Val112insTer Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Met68Ile Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Met6Thr Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Phe79Ser Single submitter ⚠
  • p.Pro146Arg Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Pro151Ser Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Pro169Leu Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Pro173Leu Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Pro187Ser Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Pro20Ser Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Pro25Ser Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Pro41Ser Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Pro73Leu Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Pro82Ser Single submitter ⚠
  • p.Pro82Thr Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Pro89fs Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Pro89Leu Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Pro95Ala Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Ser104Asn Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Ser122Pro Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Ser122Tyr Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Ser175Pro Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Ser180Arg Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Ser180Asn Single submitter ⚠
  • p.Ser181Cys Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Ser9Phe Single submitter Charcot-Marie-Tooth disease axonal type 2L
  • p.Thr176Ala Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Thr176Lys Single submitter Inborn genetic diseases ⚠
  • p.Thr194Asn Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Thr194Ser Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Thr196fs Single submitter
  • p.Thr45Arg Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Thr63Ile Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Thr76Ile Single submitter Inborn genetic diseases ⚠
  • p.Thr76Ser Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Thr87Ile Single submitter Inborn genetic diseases ⚠
  • p.Trp48Arg Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Tyr118Ter Single submitter Inborn genetic diseases
  • p.Val100Met Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Val119Leu Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Val119Met Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Val121Met Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Val135Leu Single submitter neuronopathy, distal hereditary motor, type 2A ⚠
  • p.Val149Ala Single submitter ⚠
  • p.Val154Ala Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Val171Ile Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Val81Met Single submitter Charcot-Marie-Tooth disease axonal type 2L ⚠
  • p.Ser159Thr No assertion criteria HSPB8-related disorder ⚠
  • p.Ser9Pro No assertion criteria Charcot-Marie-Tooth disease ⚠