Sugi Variant

Sugi Variant/ACAD8

ACAD8 — 299 ClinVar variants

All ClinVar germline ACAD8 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 132 flagged for review →

20 Pathogenic · 3 Pathogenic/Likely pathogenic · 13 Likely pathogenic · 23 Conflicting · 41 Benign · 4 Benign/Likely benign · 57 Likely benign · 138 Uncertain significance

Full ACAD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 132

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 10

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

Predictors lean, ClinVar uncertain 61

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

Predictors split 59

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

All ACAD8 variants

Pathogenic 20

  • p.Arg206Ter Multiple submitters Inborn genetic diseases
  • p.Arg296Ter Multiple submitters isobutyryl-CoA dehydrogenase deficiency
  • p.Gly96Ser Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • c.1092+1G>A Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.1092+1G>C Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.567+1G>A Single submitter
  • c.567+2del Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Arg244Ter Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Arg334Cys Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Arg392Ser Single submitter Inborn genetic diseases
  • p.Arg58Ter Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Cys116Ter Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Cys150fs Single submitter
  • p.Gln45Ter Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Glu197Ter Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Gly306fs Single submitter
  • p.Leu16fs Single submitter
  • p.Ser175fs Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Tyr158Ser Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.His289Gln No assertion criteria isobutyryl-CoA dehydrogenase deficiency ⚠

Pathogenic/Likely pathogenic 3

  • p.Gly377Ser Multiple submitters isobutyryl-CoA dehydrogenase deficiency
  • p.Met128Ile Multiple submitters isobutyryl-CoA dehydrogenase deficiency
  • p.Met1Thr Multiple submitters isobutyryl-CoA dehydrogenase deficiency

Likely pathogenic 13

  • c.1092+2T>G Single submitter ACAD8-related disorder
  • c.1195+1G>A Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.1195+1G>C Single submitter
  • c.568-2A>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.939+1G>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Arg330Gln Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Cys129Tyr Single submitter
  • p.Gln414Ter Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Gln69Ter Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Met1Ile Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Met1Val Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Ser282Phe Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Val253Gly Single submitter isobutyryl-CoA dehydrogenase deficiency

Conflicting classifications of pathogenicity 23

  • c.110-9T>C Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.491-6C>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.567+12C>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.841+9C>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Ala156Ser Single submitter Inborn genetic diseases ⚠
  • p.Ala245Val Single submitter Inborn genetic diseases ⚠
  • p.Ala320Thr Single submitter ACAD8-related disorder ⚠
  • p.Arg302Gln Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Arg330Trp Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Arg58Gln Single submitter Inborn genetic diseases ⚠
  • p.Asn274Lys Single submitter ACAD8-related disorder ⚠
  • p.Asn335Ser Single submitter Inborn genetic diseases ⚠
  • p.Asp134Tyr Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Gln69= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Glu262Lys Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Gly137Arg Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Gly97Arg Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Met322Thr Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Met60Val Single submitter Inborn genetic diseases ⚠
  • p.Met78Thr Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ser411= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Tyr158Cys Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Val388Met Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠

Benign 41

Benign/Likely benign 4

  • c.210+6C>T Multiple submitters isobutyryl-CoA dehydrogenase deficiency
  • c.842-8C>G Multiple submitters isobutyryl-CoA dehydrogenase deficiency
  • p.Phe136= Multiple submitters isobutyryl-CoA dehydrogenase deficiency
  • p.Ser171Cys Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠

Likely benign 57

  • c.109+133G>C Multiple submitters
  • c.380+17G>T Multiple submitters isobutyryl-CoA dehydrogenase deficiency
  • c.491-35C>A Multiple submitters
  • c.491-36T>C Multiple submitters
  • c.567+8C>T Multiple submitters isobutyryl-CoA dehydrogenase deficiency
  • c.1093-24C>T Single submitter
  • c.110-174A>G Single submitter
  • c.110-17T>C Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.1195+10G>A Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.1195+198G>A Single submitter
  • c.1195+7_1195+8delinsTA Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.1196-9C>G Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.210+7G>A Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.211-20C>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.380+7G>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.381-9A>G Single submitter
  • c.705+12T>C Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.705+18A>G Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.706-5G>A Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.841+14G>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.842-18G>A Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.842-19C>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.939+11C>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.940-20C>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*494A>G Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*652C>G Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Ala328= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Ala52= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Ala81= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Arg12= Single submitter
  • p.Arg8= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Asn186Ser Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Asn274= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Cys205= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Gln316= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Glu66= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Gly166= Single submitter
  • p.His289= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.His28Arg Single submitter Inborn genetic diseases
  • p.His373= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Ile218Val Single submitter Inborn genetic diseases ⚠
  • p.Ile268= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Ile408= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Lys303= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Phe317= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Phe9= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Pro147= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Pro148= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Ser135Thr Single submitter Inborn genetic diseases
  • p.Ser282= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Ser4= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Thr207= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Tyr376= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Tyr382= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Tyr387= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Val270Met Single submitter Inborn genetic diseases
  • p.Val95= Single submitter isobutyryl-CoA dehydrogenase deficiency

Uncertain significance 138

  • c.1092+3_1092+6del Multiple submitters isobutyryl-CoA dehydrogenase deficiency
  • c.841+6A>C Multiple submitters Inborn genetic diseases
  • c.940-13C>G Multiple submitters isobutyryl-CoA dehydrogenase deficiency
  • p.Ala113Thr Multiple submitters Inborn genetic diseases ⚠
  • p.Ala269Val Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ala329Thr Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ala383Thr Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Arg102His Multiple submitters Inborn genetic diseases ⚠
  • p.Arg244Gly Multiple submitters Inborn genetic diseases ⚠
  • p.Arg296Gln Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Arg79Gly Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Asp346Asn Multiple submitters Inborn genetic diseases ⚠
  • p.Gln385Arg Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Glu44Lys Multiple submitters Inborn genetic diseases ⚠
  • p.Gly374Arg Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ile123Lys Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ile215Val Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Leu84Val Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Met152Thr Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ser165Thr Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Thr161Ala Multiple submitters isobutyryl-CoA dehydrogenase deficiency ⚠
  • c.109+19G>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.110-13A>G Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.110-6C>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.1196-4_1196-2del Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.380+7G>A Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.381-4T>A Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.841+15G>A Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.842-15G>A Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*238G>C Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*266T>A Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*306C>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*351C>G Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*441C>G Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*608G>A Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*622C>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*634T>C Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*696A>G Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*69G>T Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*705T>G Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*82G>C Single submitter isobutyryl-CoA dehydrogenase deficiency
  • c.*874C>G Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Ala11Glu Single submitter Inborn genetic diseases ⚠
  • p.Ala11Val Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ala176Gly Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ala195Asp Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ala287Pro Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ala288Thr Single submitter ⚠
  • p.Ala290Pro Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ala290Thr Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ala310Thr Single submitter ⚠
  • p.Ala329Val Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ala364= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Arg102Leu Single submitter Inborn genetic diseases ⚠
  • p.Arg102Pro Single submitter Inborn genetic diseases ⚠
  • p.Arg206Gln Single submitter ⚠
  • p.Arg206Gly Single submitter ⚠
  • p.Arg244Gln Single submitter ⚠
  • p.Arg29Trp Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Arg302Pro Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Arg79Gln Single submitter Inborn genetic diseases ⚠
  • p.Cys150Tyr Single submitter Inborn genetic diseases ⚠
  • p.Cys217Gly Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Cys283Trp Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Cys362Arg Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Cys366Tyr Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Gln141Arg Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Gln179Arg Single submitter Inborn genetic diseases ⚠
  • p.Gln304Arg Single submitter Inborn genetic diseases ⚠
  • p.Gln386Arg Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Gln92Arg Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Glu153= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Glu162Lys Single submitter Inborn genetic diseases ⚠
  • p.Glu398Gly Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Gly115Asp Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Gly14Ser Single submitter Inborn genetic diseases ⚠
  • p.Gly180Arg Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Gly265Ala Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Gly276Glu Single submitter Inborn genetic diseases ⚠
  • p.Gly27Ser Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Gly286Arg Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Gly87Arg Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Gly87Glu Single submitter ⚠
  • p.Gly97Glu Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ile125Met Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ile200Asn Single submitter Inborn genetic diseases ⚠
  • p.Ile247Thr Single submitter Inborn genetic diseases ⚠
  • p.Ile278Thr Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ile35Ser Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ile408Thr Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Leu103Arg Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Leu13Val Single submitter Inborn genetic diseases ⚠
  • p.Leu285= Single submitter
  • p.Leu299Phe Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Leu326Gln Single submitter ⚠
  • p.Leu41Ile Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Leu72Met Single submitter Inborn genetic diseases ⚠
  • p.Lys144= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Lys144Arg Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Lys177Glu Single submitter Inborn genetic diseases ⚠
  • p.Lys189Asn Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Lys380Gln Single submitter Inborn genetic diseases ⚠
  • p.Met204Thr Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Met322Arg Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Met322Val Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Met353Thr Single submitter ⚠
  • p.Met353Val Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Met372Ile Single submitter Inborn genetic diseases ⚠
  • p.Phe109Ser Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Phe136Leu Single submitter Inborn genetic diseases ⚠
  • p.Phe229Leu Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Phe9Tyr Single submitter Inborn genetic diseases ⚠
  • p.Pro148Leu Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Pro37Ser Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ser106Pro Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ser124Arg Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ser165Ile Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ser175= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Ser261Asn Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ser33= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Ser352Pro Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ser352Thr Single submitter Inborn genetic diseases ⚠
  • p.Ser4Arg Single submitter Inborn genetic diseases ⚠
  • p.Ser98Phe Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Ser98Pro Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Thr114Ala Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Thr117Ile Single submitter Inborn genetic diseases ⚠
  • p.Thr119Ile Single submitter Inborn genetic diseases ⚠
  • p.Thr151= Single submitter isobutyryl-CoA dehydrogenase deficiency
  • p.Thr161Ile Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Thr224Ala Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Thr32Asn Single submitter Inborn genetic diseases ⚠
  • p.Tyr378Asn Single submitter Inborn genetic diseases ⚠
  • p.Tyr378Ser Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Val202Glu Single submitter ⚠
  • p.Val203Ile Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Val22Phe Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠
  • p.Val255Met Single submitter isobutyryl-CoA dehydrogenase deficiency ⚠