Sugi Variant

Sugi Variant/TWNK

TWNK — 681 ClinVar variants

All ClinVar germline TWNK variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 359 flagged for review →

36 Pathogenic · 13 Pathogenic/Likely pathogenic · 31 Likely pathogenic · 64 Conflicting · 11 Benign · 5 Benign/Likely benign · 163 Likely benign · 358 Uncertain significance

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

⚑ Evidence disagreements 359

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 14

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

Predictors agree, ClinVar conflicts 27

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

Predictors lean, ClinVar uncertain 231

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 231

Predictors split 87

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

All TWNK variants

Pathogenic 36

  • p.Arg29Ter Multiple submitters
  • p.Phe370Leu Multiple submitters ⚠
  • p.Phe488fs Multiple submitters
  • p.Ser369Tyr Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Trp474Cys Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1
  • p.Ala318Thr Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type) ⚠
  • p.Ala460Gly Single submitter ⚠
  • p.Ala577fs Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type)
  • p.Arg196Ter Single submitter
  • p.Arg329Ter Single submitter
  • p.Arg334Pro Single submitter ⚠
  • p.Arg354Pro Single submitter Possible mitochondrial disorder - nuclear genes
  • p.Arg406Ter Single submitter
  • p.Arg6Ter Single submitter
  • p.Gln458fs Single submitter
  • p.Gln458His Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Gly442_Ser443insTer Single submitter
  • p.His512fs Single submitter
  • p.Leu17fs Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type)
  • p.Leu360Gly Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Lys319Thr Single submitter ⚠
  • p.Phe100fs Single submitter
  • p.Phe248fs Single submitter Perrault syndrome 5
  • p.Phe321fs Single submitter
  • p.Ser232_Tyr233insTer Single submitter
  • p.Trp441Gly Single submitter Perrault syndrome 5
  • p.Val173fs Single submitter
  • c.1485-1G>A No assertion criteria third-degree atrioventricular block
  • p.Ala475Pro No assertion criteria progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.His364_Lys365insLeuSerArgIleLeuArgThrAlaLeuProAlaTrpHis No assertion criteria progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Leu112fs No assertion criteria mitochondrial DNA depletion syndrome 7 (hepatocerebral type)
  • p.Leu381Pro No assertion criteria mitochondrial disease
  • p.Leu464Pro No assertion criteria mitochondrial disease
  • p.Lys319Glu No assertion criteria progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 ⚠
  • p.Thr457Ile No assertion criteria mitochondrial DNA depletion syndrome 7 (hepatocerebral type)
  • p.Trp315Leu No assertion criteria progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 ⚠

Pathogenic/Likely pathogenic 13

  • p.Ala359Thr Multiple submitters TWNK-related disorder ⚠
  • p.Arg217Ter Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Arg285Ter Multiple submitters TWNK-related disorder
  • p.Arg303Trp Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 ⚠
  • p.Arg323Ter Multiple submitters mitochondrial DNA depletion syndrome 7 (hepatocerebral type)
  • p.Arg334Gln Multiple submitters mitochondrial DNA depletion syndrome 7 (hepatocerebral type) ⚠
  • p.Arg357Pro Multiple submitters TWNK-related disorder
  • p.Arg374Gln Multiple submitters progressive external ophthalmoplegia ⚠
  • p.Arg374Trp Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Asn448Asp Multiple submitters
  • p.Asn585Ser Multiple submitters Perrault syndrome 5
  • p.Phe478Cys Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Tyr508Cys Multiple submitters C10ORF2 & TWNK-related disorders ⚠

Likely pathogenic 31

  • p.Arg400Cys Multiple submitters mitochondrial DNA depletion syndrome 7 (hepatocerebral type) ⚠
  • p.Phe485Ile Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Ala345Ser Single submitter ⚠
  • p.Ala359Val Single submitter ⚠
  • p.Ala460Pro Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Ala85fs Single submitter TWNK-related disorder
  • p.Arg192Cys Single submitter mitochondrial hepatopathy ⚠
  • p.Arg199Ter Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type)
  • p.Arg240Ter Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Arg25fs Single submitter
  • p.Arg334Ter Single submitter
  • p.Arg374Leu Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Arg400Leu Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type)
  • p.Arg463Gln Single submitter auditory neuropathy ⚠
  • p.Asn438Lys Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type)
  • p.Gln467Ter Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type)
  • p.Gln590Ter Single submitter
  • p.Glu479Ala Single submitter ⚠
  • p.Glu479Lys Single submitter
  • p.Gly23fs Single submitter
  • p.His67fs Single submitter
  • p.Leu14fs Single submitter Perrault syndrome 5
  • p.Leu410Arg Single submitter
  • p.Leu481Val Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type) ⚠
  • p.Met455Thr Single submitter
  • p.Met455Val Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Ser426fs Single submitter Perrault syndrome 5
  • p.Thr411Met Single submitter mitochondrial hepatopathy
  • p.Trp315Cys Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 ⚠
  • p.Trp474Ter Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Val333Met Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3

Conflicting classifications of pathogenicity 64

  • c.1244-14C>T Single submitter autosomal recessive cerebellar ataxia
  • c.1735-14C>A Single submitter autosomal recessive cerebellar ataxia
  • c.1735-3del Single submitter Inborn genetic diseases
  • c.-290G>C Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • c.-650A>G Single submitter autosomal recessive cerebellar ataxia
  • c.*204G>A Single submitter sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
  • c.*301C>T Single submitter sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
  • c.*419A>T Single submitter sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
  • p.Ala145Val Single submitter ⚠
  • p.Ala224= Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type)
  • p.Ala318= Single submitter
  • p.Ala362Pro Single submitter mitochondrial disease ⚠
  • p.Ala533Thr Single submitter autosomal recessive cerebellar ataxia ⚠
  • p.Ala57Thr Single submitter Inborn genetic diseases ⚠
  • p.Ala659Thr Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type) ⚠
  • p.Arg160Ter Single submitter Perrault syndrome 5
  • p.Arg265Cys Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type) ⚠
  • p.Arg302Trp Single submitter C10ORF2-related disorders ⚠
  • p.Arg303Gln Single submitter Possible mitochondrial disorder - nuclear genes ⚠
  • p.Arg334Leu Single submitter ⚠
  • p.Arg341Cys Single submitter ⚠
  • p.Arg354Cys Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type) ⚠
  • p.Arg371Trp Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 ⚠
  • p.Arg391Cys Single submitter ⚠
  • p.Arg391His Single submitter C10ORF2 & TWNK-related disorders ⚠
  • p.Arg406Gln Single submitter auditory neuropathy ⚠
  • p.Arg463Trp Single submitter Possible mitochondrial disorder - nuclear genes ⚠
  • p.Arg495= Single submitter
  • p.Arg543Gln Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type) ⚠
  • p.Arg601Gln Single submitter Perrault syndrome ⚠
  • p.Arg609= Single submitter
  • p.Arg65Trp Single submitter Perrault syndrome 5 ⚠
  • p.Arg682His Single submitter autosomal recessive cerebellar ataxia ⚠
  • p.Asn246Ser Single submitter Perrault syndrome 5 ⚠
  • p.Asn399Ser Single submitter autosomal recessive cerebellar ataxia ⚠
  • p.Asn448Ser Single submitter ⚠
  • p.Asn549Ser Single submitter ⚠
  • p.Asp188Asn Single submitter ⚠
  • p.Glu479Gly Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 ⚠
  • p.Gly19Glu Single submitter autosomal recessive cerebellar ataxia ⚠
  • p.Gly213= Single submitter autosomal recessive cerebellar ataxia
  • p.Gly230Val Single submitter hereditary spastic paraplegia ⚠
  • p.Gly26Ser Single submitter sensory ataxic neuropathy, dysarthria, and ophthalmoparesis ⚠
  • p.Gly348Arg Single submitter Inborn genetic diseases ⚠
  • p.Gly540Arg Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type) ⚠
  • p.His524= Single submitter autosomal recessive cerebellar ataxia
  • p.Ile367= Single submitter sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
  • p.Leu164= Single submitter sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
  • p.Leu308= Single submitter sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
  • p.Leu81Val Single submitter mitochondrial DNA depletion syndrome 7 (hepatocerebral type) ⚠
  • p.Lys566Arg Single submitter autosomal recessive cerebellar ataxia ⚠
  • p.Lys651= Single submitter autosomal recessive cerebellar ataxia
  • p.Lys684Gln Single submitter Inborn genetic diseases ⚠
  • p.Met114Leu Single submitter ⚠
  • p.Phe395Leu Single submitter ⚠
  • p.Pro292Thr Single submitter Perrault syndrome 5 ⚠
  • p.Pro335Thr Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 ⚠
  • p.Ser128= Single submitter autosomal recessive cerebellar ataxia
  • p.Ser653Phe Single submitter Perrault syndrome 5 ⚠
  • p.Thr276Met Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 ⚠
  • p.Thr358= Single submitter
  • p.Thr496= Single submitter autosomal recessive cerebellar ataxia
  • p.Tyr537His Single submitter progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 ⚠
  • p.Val507Ile Single submitter Perrault syndrome 5 ⚠

Benign 11

  • c.1593-3T>C Multiple submitters autosomal recessive cerebellar ataxia
  • c.1593-5C>T Multiple submitters autosomal recessive cerebellar ataxia
  • c.1734+16C>A Multiple submitters
  • c.1734+84G>A Multiple submitters
  • c.-605G>T Multiple submitters autosomal recessive cerebellar ataxia
  • c.*521C>G Multiple submitters sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
  • c.*766A>T Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Val368Ile Multiple submitters hereditary spastic paraplegia
  • c.1485-259_1485-254del Single submitter
  • c.1735-202G>A Single submitter
  • p.Gly26Ala Single submitter

Benign/Likely benign 5

  • c.1734+17G>A Multiple submitters
  • c.*455C>T Multiple submitters autosomal recessive cerebellar ataxia
  • p.Asp509= Multiple submitters progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3
  • p.Ile532= Multiple submitters hereditary spastic paraplegia
  • p.Leu267= Multiple submitters

Likely benign 163

Uncertain significance 358

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