Sugi Variant

Sugi Variant/FBXL4

FBXL4 — 632 ClinVar variants

All ClinVar germline FBXL4 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 304 flagged for review →

31 Pathogenic · 13 Pathogenic/Likely pathogenic · 39 Likely pathogenic · 78 Conflicting · 17 Benign · 4 Benign/Likely benign · 94 Likely benign · 356 Uncertain significance

Full FBXL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 304

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 3

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

Predictors agree, ClinVar conflicts 20

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

Predictors lean, ClinVar uncertain 217

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 217

Predictors split 64

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

All FBXL4 variants

Pathogenic 31

Pathogenic/Likely pathogenic 13

  • c.859-1G>T Multiple submitters mitochondrial DNA depletion syndrome 13
  • p.Arg206Ter Multiple submitters FBXL4-related disorder
  • p.Arg22Ter Multiple submitters FBXL4-related disorder
  • p.Arg430Ter Multiple submitters mitochondrial DNA depletion syndrome 13
  • p.Arg435Gln Multiple submitters Inborn genetic diseases ⚠
  • p.Arg482Trp Multiple submitters Inborn genetic diseases ⚠
  • p.Arg98Ter Multiple submitters FBXL4-related disorder
  • p.Cys411Tyr Multiple submitters mitochondrial DNA depletion syndrome 13
  • p.Gln124Ter Multiple submitters FBXL4-related disorder
  • p.Gly568Ala Multiple submitters developmental and epileptic encephalopathy, 85, with or without midline brain defects ⚠
  • p.Ile566Met Multiple submitters mitochondrial DNA depletion syndrome 13 ⚠
  • p.Leu481fs Multiple submitters mitochondrial DNA depletion syndrome 13
  • p.Val140Ala Multiple submitters mitochondrial DNA depletion syndrome 13 ⚠

Likely pathogenic 39

  • p.Arg435Leu Multiple submitters mitochondrial DNA depletion syndrome 13
  • p.Asp565Gly Multiple submitters mitochondrial DNA depletion syndrome 13 ⚠
  • p.Ile205Thr Multiple submitters mitochondrial DNA depletion syndrome 13 ⚠
  • p.Leu481Pro Multiple submitters mitochondrial DNA depletion syndrome 13
  • p.Pro275_Asn276insTer Multiple submitters mitochondrial DNA depletion syndrome 13
  • p.Pro516_Ser521del Multiple submitters mitochondrial DNA depletion syndrome 13
  • p.Trp514Gly Multiple submitters FBXL4-related disorder
  • c.1390-2A>G Single submitter FBXL4-related disorder
  • c.1703-2A>G Single submitter mitochondrial DNA depletion syndrome 13
  • c.858+5G>C Single submitter mitochondrial DNA depletion syndrome 13
  • p.Ala139fs Single submitter mitochondrial DNA depletion syndrome 13
  • p.Ala442fs Single submitter mitochondrial DNA depletion syndrome 13
  • p.Ala471Thr Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Asp221His Single submitter mitochondrial DNA depletion syndrome 13
  • p.Asp466_Tyr467insTer Single submitter mitochondrial DNA depletion syndrome 13
  • p.Asp550fs Single submitter mitochondrial DNA depletion syndrome 13
  • p.Asp591Gly Single submitter mitochondrial DNA depletion syndrome 13
  • p.Cys301Ter Single submitter mitochondrial DNA depletion syndrome 13
  • p.Cys411Ser Single submitter ⚠
  • p.Cys450Trp Single submitter mitochondrial DNA depletion syndrome 13
  • p.Cys515fs Single submitter Leigh syndrome
  • p.Cys584Arg Single submitter mitochondrial DNA depletion syndrome 13
  • p.Gln454Ter Single submitter mitochondrial DNA depletion syndrome 13
  • p.Glu338Ter Single submitter mitochondrial DNA depletion syndrome
  • p.Gly101Arg Single submitter mitochondrial DNA depletion syndrome 13
  • p.Gly66Glu Single submitter mitochondrial DNA depletion syndrome 13
  • p.Ile566Val Single submitter ⚠
  • p.Leu581del Single submitter Inborn genetic diseases
  • p.Lys479fs Single submitter Leigh syndrome
  • p.Ser410Phe Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Thr202Arg Single submitter mitochondrial DNA depletion syndrome 13
  • p.Thr74fs Single submitter FBXL4-related disorder
  • p.Tyr100Cys Single submitter mitochondrial DNA depletion syndrome 13
  • p.Val140fs Single submitter mitochondrial DNA depletion syndrome 13
  • p.Val613fs Single submitter mitochondrial DNA depletion syndrome 13
  • p.Val613Glu Single submitter mitochondrial DNA depletion syndrome 13
  • p.Cys584fs No assertion criteria mitochondrial DNA depletion syndrome 13
  • p.Gln536Pro No assertion criteria ⚠
  • p.Ser596fs No assertion criteria mitochondrial DNA depletion syndrome 13

Conflicting classifications of pathogenicity 78

  • c.1103+13C>G Single submitter mitochondrial DNA depletion syndrome 13
  • c.1103+13C>T Single submitter mitochondrial DNA depletion syndrome 13
  • c.1103+7A>G Single submitter mitochondrial DNA depletion syndrome 13
  • c.1104-13G>T Single submitter mitochondrial DNA depletion syndrome 13
  • c.1104-19T>C Single submitter mitochondrial DNA depletion syndrome 13
  • c.1104-4G>T Single submitter mitochondrial DNA depletion syndrome 13
  • c.1317+14A>G Single submitter mitochondrial DNA depletion syndrome 13
  • c.1317+19T>G Single submitter mitochondrial DNA depletion syndrome 13
  • c.1318-15G>C Single submitter mitochondrial DNA depletion syndrome 13
  • c.1318-16T>C Single submitter mitochondrial DNA depletion syndrome 13
  • c.1389+11G>A Single submitter mitochondrial DNA depletion syndrome 13
  • c.1389+13G>C Single submitter mitochondrial DNA depletion syndrome 13
  • c.1389+18C>A Single submitter mitochondrial DNA depletion syndrome 13
  • c.1390-1G>A Single submitter
  • c.1702+11A>T Single submitter mitochondrial DNA depletion syndrome 13
  • c.1702+18A>G Single submitter mitochondrial DNA depletion syndrome 13
  • c.1703-14T>C Single submitter mitochondrial DNA depletion syndrome 13
  • c.513-13C>G Single submitter mitochondrial DNA depletion syndrome 13
  • c.*9A>G Single submitter mitochondrial DNA depletion syndrome 13
  • p.Ala26= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Ala418= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Ala418Pro Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Ala529Glu Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Ala575Ser Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Arg22Gln Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Arg302= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Arg358Lys Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Arg379Cys Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Arg482Gln Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Arg488= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Asn83= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Asp221Val Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Asp245= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Asp248= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Asp249= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Asp249Glu Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Asp552= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Asp591Ala Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Cys558Tyr Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Gln312= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Gln417= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Gln519Ter Single submitter mitochondrial DNA depletion syndrome 13
  • p.Gln563= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Gln597Pro Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Gly149Arg Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Gly256Ser Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Gly274= Single submitter mitochondrial DNA depletion syndrome 13
  • p.His35Arg Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Ile246Thr Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Ile361= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Ile551Asn Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Leu234= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Leu337= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Leu340= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Leu352= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Leu403= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Leu506= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Leu567= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Leu577= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Pro180= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Pro574= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Ser261Asn Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Ser375= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Ser42Asn Single submitter Inborn genetic diseases ⚠
  • p.Ser45= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Ser451= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Ser588= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Thr117= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Thr181Ala Single submitter mitochondrial DNA depletion syndrome 13 ⚠
  • p.Thr238= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Thr27Ala Single submitter Inborn genetic diseases ⚠
  • p.Thr483= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Thr522= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Thr541Ile Single submitter FBXL4-related disorder ⚠
  • p.Tyr100= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Tyr16= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Tyr73= Single submitter mitochondrial DNA depletion syndrome 13
  • p.Val84= Single submitter mitochondrial DNA depletion syndrome 13

Benign 17

Benign/Likely benign 4

  • c.1703-36TGTTT[6] Multiple submitters
  • c.*5A>G Multiple submitters mitochondrial DNA depletion syndrome 13
  • p.Ala156= Multiple submitters mitochondrial DNA depletion syndrome 13
  • p.Leu143= Multiple submitters mitochondrial DNA depletion syndrome 13

Likely benign 94

Uncertain significance 356

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