ACSL4 — 197 ClinVar variants
All ClinVar germline ACSL4 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 126 flagged for review →
6 Pathogenic · 8 Likely pathogenic · 12 Conflicting · 13 Benign · 2 Benign/Likely benign · 28 Likely benign · 128 Uncertain significance
Full ACSL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 126
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 1
ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.
-
ACSL4 p.Ser158Tyr
Likely pathogenic
No assertion criteria
intellectual disability, X-linked 63
Predictors agree, ClinVar conflicts 4
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
-
ACSL4 p.Arg529His
Conflicting
Single submitter
intellectual disability, X-linked 63
-
ACSL4 p.Ile30Met
Conflicting
Single submitter
Inborn genetic diseases
-
ACSL4 p.Met330Thr
Conflicting
Single submitter
intellectual disability, X-linked 63
-
ACSL4 p.Pro135Leu
Conflicting
Single submitter
Inborn genetic diseases
Predictors lean, ClinVar uncertain 60
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
-
ACSL4 p.Arg631Gln
Uncertain significance
Multiple submitters
intellectual disability, X-linked 63
-
ACSL4 p.Asn95Asp
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
ACSL4 p.Asn95Ser
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
ACSL4 p.His23Arg
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
ACSL4 p.Lys271Arg
Uncertain significance
Multiple submitters
intellectual disability, X-linked 63
-
ACSL4 p.Pro404Leu
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
ACSL4 p.Ser501Tyr
Uncertain significance
Multiple submitters
Inborn genetic diseases
- ACSL4 c.-12-104T>G Uncertain significance Single submitter
- ACSL4 c.-12-2A>G Uncertain significance Single submitter
- ACSL4 c.-12-53C>G Uncertain significance Single submitter
- ACSL4 c.-12-7T>G Uncertain significance Single submitter
- ACSL4 p.Ala103Val Uncertain significance Single submitter
- ACSL4 p.Ala232Val Uncertain significance Single submitter
- ACSL4 p.Ala28Ser Uncertain significance Single submitter
-
ACSL4 p.Ala433Gly
Uncertain significance
Single submitter
Inborn genetic diseases
-
ACSL4 p.Ala616Ser
Uncertain significance
Single submitter
intellectual disability, X-linked 63
- ACSL4 p.Ala647Val Uncertain significance Single submitter
- ACSL4 p.Arg396Gly Uncertain significance Single submitter
- ACSL4 p.Arg396His Uncertain significance Single submitter
- ACSL4 p.Arg475Ser Uncertain significance Single submitter
- ACSL4 p.Arg529Gly Uncertain significance Single submitter
-
ACSL4 p.Asn86Ser
Uncertain significance
Single submitter
Inborn genetic diseases
-
ACSL4 p.Glu350Gly
Uncertain significance
Single submitter
Inborn genetic diseases
- ACSL4 p.Gly144Ser Uncertain significance Single submitter
- ACSL4 p.Gly15Glu Uncertain significance Single submitter
-
ACSL4 p.Gly373Arg
Uncertain significance
Single submitter
Inborn genetic diseases
- ACSL4 p.Gly432Asp Uncertain significance Single submitter
- ACSL4 p.Gly488Arg Uncertain significance Single submitter
- ACSL4 p.Gly539Arg Uncertain significance Single submitter
-
ACSL4 p.His23Tyr
Uncertain significance
Single submitter
intellectual disability, X-linked 63
- ACSL4 p.Ile178Thr Uncertain significance Single submitter
-
ACSL4 p.Ile255Leu
Uncertain significance
Single submitter
Inborn genetic diseases
- ACSL4 p.Ile299Val Uncertain significance Single submitter
- ACSL4 p.Ile32Val Uncertain significance Single submitter
-
ACSL4 p.Ile626Val
Uncertain significance
Single submitter
Inborn genetic diseases
- ACSL4 p.Leu367Ser Uncertain significance Single submitter
- ACSL4 p.Leu382Ser Uncertain significance Single submitter
- ACSL4 p.Leu61Val Uncertain significance Single submitter
- ACSL4 p.Lys51Glu Uncertain significance Single submitter
- ACSL4 p.Lys661Gln Uncertain significance Single submitter
- ACSL4 p.Lys75Thr Uncertain significance Single submitter
- ACSL4 p.Met235Thr Uncertain significance Single submitter
- ACSL4 p.Met258Arg Uncertain significance Single submitter
-
ACSL4 p.Phe49Tyr
Uncertain significance
Single submitter
Inborn genetic diseases
- ACSL4 p.Pro244Leu Uncertain significance Single submitter
- ACSL4 p.Pro304Leu Uncertain significance Single submitter
-
ACSL4 p.Pro304Ser
Uncertain significance
Single submitter
intellectual disability, X-linked 63
- ACSL4 p.Pro377Ser Uncertain significance Single submitter
- ACSL4 p.Pro404Gln Uncertain significance Single submitter
- ACSL4 p.Pro627Ser Uncertain significance Single submitter
- ACSL4 p.Ser501Phe Uncertain significance Single submitter
-
ACSL4 p.Thr111Asn
Uncertain significance
Single submitter
intellectual disability
- ACSL4 p.Thr496Ile Uncertain significance Single submitter
- ACSL4 p.Trp461Cys Uncertain significance Single submitter
- ACSL4 p.Trp637Leu Uncertain significance Single submitter
- ACSL4 p.Tyr140Cys Uncertain significance Single submitter
- ACSL4 p.Tyr159Phe Uncertain significance Single submitter
- ACSL4 p.Val591Ile Uncertain significance Single submitter
-
ACSL4 p.Asn484His
Uncertain significance
No assertion criteria
intellectual disability, X-linked 63
-
ACSL4 p.Thr241Ala
Uncertain significance
No assertion criteria
intellectual disability, X-linked 63
Predictors split 61
The independent predictors disagree with each other — read with care.
-
ACSL4 p.Asn153Ser
Benign/Likely benign
Multiple submitters
Inborn genetic diseases
-
ACSL4 p.Asp521Asn
Uncertain significance
Multiple submitters
intellectual disability, X-linked 63
-
ACSL4 p.Cys129Ser
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
ACSL4 p.His150Leu
Uncertain significance
Multiple submitters
autism spectrum disorder
-
ACSL4 p.Lys388Arg
Uncertain significance
Multiple submitters
intellectual disability, X-linked 63
- ACSL4 p.Pro472Ala Uncertain significance Multiple submitters
-
ACSL4 p.Tyr132Cys
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
ACSL4 p.Tyr82Phe
Likely benign
Multiple submitters
Inborn genetic diseases
-
ACSL4 c.-10G>T
Uncertain significance
Single submitter
intellectual disability, X-linked 63
- ACSL4 p.Ala497Val Uncertain significance Single submitter
-
ACSL4 p.Arg92Cys
Likely benign
Single submitter
Inborn genetic diseases
-
ACSL4 p.Arg92His
Conflicting
Single submitter
Inborn genetic diseases
- ACSL4 p.Asn253Ser Uncertain significance Single submitter
-
ACSL4 p.Asn343Thr
Uncertain significance
Single submitter
intellectual disability, X-linked 63
- ACSL4 p.Asn394Asp Benign Single submitter
-
ACSL4 p.Asn473Asp
Uncertain significance
Single submitter
intellectual disability, X-linked 63
-
ACSL4 p.Asn473Lys
Uncertain significance
Single submitter
Inborn genetic diseases
- ACSL4 p.Asn96Ile Uncertain significance Single submitter
-
ACSL4 p.Asp12Gly
Uncertain significance
Single submitter
Inborn genetic diseases
-
ACSL4 p.Asp177Gly
Uncertain significance
Single submitter
Inborn genetic diseases
- ACSL4 p.Asp25Asn Uncertain significance Single submitter
-
ACSL4 p.Asp503Gly
Conflicting
Single submitter
ACSL4-related disorder
- ACSL4 p.Asp597Gly Uncertain significance Single submitter
-
ACSL4 p.Gln349Arg
Uncertain significance
Single submitter
Inborn genetic diseases
-
ACSL4 p.Gln462Arg
Uncertain significance
Single submitter
Inborn genetic diseases
-
ACSL4 p.Gln588His
Uncertain significance
Single submitter
Inborn genetic diseases
-
ACSL4 p.Glu156Asp
Uncertain significance
Single submitter
intellectual disability, X-linked 63
- ACSL4 p.Glu210Gly Uncertain significance Single submitter
- ACSL4 p.Glu494Asp Uncertain significance Single submitter
- ACSL4 p.Gly105Arg Uncertain significance Single submitter
- ACSL4 p.Gly465Cys Uncertain significance Single submitter
-
ACSL4 p.His183Leu
Likely benign
Single submitter
Inborn genetic diseases
- ACSL4 p.His658Arg Uncertain significance Single submitter
-
ACSL4 p.Ile275Val
Conflicting
Single submitter
Inborn genetic diseases
- ACSL4 p.Ile32Met Uncertain significance Single submitter
- ACSL4 p.Leu160Met Uncertain significance Single submitter
- ACSL4 p.Leu286Val Uncertain significance Single submitter
- ACSL4 p.Leu79Phe Uncertain significance Single submitter
- ACSL4 p.Lys109Asn Uncertain significance Single submitter
- ACSL4 p.Met206Val Uncertain significance Single submitter
- ACSL4 p.Met330Ile Uncertain significance Single submitter
- ACSL4 p.Met345Thr Uncertain significance Single submitter
-
ACSL4 p.Met351Val
Uncertain significance
Single submitter
intellectual disability, X-linked 63
- ACSL4 p.Met487Val Uncertain significance Single submitter
- ACSL4 p.Phe201Cys Uncertain significance Single submitter
-
ACSL4 p.Pro135Ala
Uncertain significance
Single submitter
Inborn genetic diseases
-
ACSL4 p.Pro17Ser
Likely benign
Single submitter
Inborn genetic diseases
-
ACSL4 p.Pro270Leu
Likely benign
Single submitter
Inborn genetic diseases
- ACSL4 p.Pro636Ser Uncertain significance Single submitter
- ACSL4 p.Pro9Ser Uncertain significance Single submitter
- ACSL4 p.Ser163Thr Likely benign Single submitter
- ACSL4 p.Ser16Ile Uncertain significance Single submitter
- ACSL4 p.Ser291Tyr Uncertain significance Single submitter
- ACSL4 p.Thr227Met Likely benign Single submitter
- ACSL4 p.Thr22Ile Uncertain significance Single submitter
- ACSL4 p.Thr357Asn Uncertain significance Single submitter
- ACSL4 p.Tyr186His Uncertain significance Single submitter
- ACSL4 p.Tyr341Cys Uncertain significance Single submitter
- ACSL4 p.Tyr341Ser Uncertain significance Single submitter
-
ACSL4 p.Tyr442Cys
Conflicting
Single submitter
Inborn genetic diseases
-
ACSL4 p.Lys40Asn
Uncertain significance
No assertion criteria
ACSL4-related disorder
All ACSL4 variants
Pathogenic 6
- p.Arg243Ter Single submitter
- p.His282fs Single submitter
- p.Leu268fs Single submitter intellectual disability, X-linked 63
- p.Met413fs Single submitter intellectual disability, X-linked 63
- c.1003-2A>G No assertion criteria intellectual disability, X-linked 63
- p.Arg529Ser No assertion criteria intellectual disability, X-linked 63
Likely pathogenic 8
- c.1315+1G>A Single submitter intellectual disability, X-linked 63
- p.Glu210fs Single submitter intellectual disability, X-linked 63
- p.Leu358fs Single submitter intellectual disability, X-linked 63
- p.Lys552Ter Single submitter intellectual disability, X-linked 63
- p.Pro334Leu Single submitter intellectual disability, X-linked 63
- p.Val571Gly Single submitter intellectual disability
- p.Asn86fs No assertion criteria intellectual disability, X-linked 63
- p.Ser158Tyr No assertion criteria intellectual disability, X-linked 63 ⚠
Conflicting classifications of pathogenicity 12
- c.1391-7T>C Single submitter non-syndromic X-linked intellectual disability
- c.1698-10G>A Single submitter non-syndromic X-linked intellectual disability
- c.806+3A>G Single submitter Inborn genetic diseases
- c.806+8A>C Single submitter
- p.Arg529His Single submitter intellectual disability, X-linked 63 ⚠
- p.Arg92His Single submitter Inborn genetic diseases ⚠
- p.Asp503Gly Single submitter ACSL4-related disorder ⚠
- p.Ile275Val Single submitter Inborn genetic diseases ⚠
- p.Ile30Met Single submitter Inborn genetic diseases ⚠
- p.Met330Thr Single submitter intellectual disability, X-linked 63 ⚠
- p.Pro135Leu Single submitter Inborn genetic diseases ⚠
- p.Tyr442Cys Single submitter Inborn genetic diseases ⚠
Benign 13
- c.1391-39G>T Multiple submitters
- c.1697+31G>A Multiple submitters intellectual disability, X-linked 63
- c.1856-9T>C Multiple submitters
- c.931-55A>G Multiple submitters
- c.931-71T>C Multiple submitters
- c.*54C>T Multiple submitters
- c.656-192T>A Single submitter
- p.Asn394Asp Single submitter ⚠
- p.Gly300= Single submitter
- p.Leu38= Single submitter
- p.Ser311= Single submitter
- p.Thr638= Single submitter Inborn genetic diseases
- c.-12-40C>T No assertion criteria ACSL4-related disorder
Benign/Likely benign 2
- c.517-24dup Multiple submitters intellectual disability, X-linked 63
- p.Asn153Ser Multiple submitters Inborn genetic diseases ⚠
Likely benign 28
- c.516+8T>G Multiple submitters intellectual disability, X-linked 63
- p.Asn492= Multiple submitters
- p.Asp503= Multiple submitters Inborn genetic diseases
- p.Gly213= Multiple submitters
- p.Ile485Val Multiple submitters intellectual disability
- p.Pro304= Multiple submitters Inborn genetic diseases
- p.Pro404= Multiple submitters Inborn genetic diseases
- p.Tyr82Phe Multiple submitters Inborn genetic diseases ⚠
- c.1002+10G>T Single submitter
- c.1855+11A>G Single submitter
- c.517-6C>T Single submitter
- p.Ala618Thr Single submitter Inborn genetic diseases
- p.Arg92Cys Single submitter Inborn genetic diseases ⚠
- p.Gly476= Single submitter Inborn genetic diseases
- p.Gly98= Single submitter
- p.His183Leu Single submitter Inborn genetic diseases ⚠
- p.Ile421Val Single submitter Inborn genetic diseases
- p.Ile557Val Single submitter Inborn genetic diseases
- p.Leu358= Single submitter Inborn genetic diseases
- p.Pro17Ser Single submitter Inborn genetic diseases ⚠
- p.Pro270Leu Single submitter Inborn genetic diseases ⚠
- p.Pro520= Single submitter Inborn genetic diseases
- p.Ser163Thr Single submitter ⚠
- p.Thr227Met Single submitter ⚠
- p.Tyr541= Single submitter
- p.Tyr570= Single submitter Inborn genetic diseases
- p.Val29Ala Single submitter Inborn genetic diseases
- p.Val596= Single submitter Inborn genetic diseases
Uncertain significance 128
- p.Arg631Gln Multiple submitters intellectual disability, X-linked 63 ⚠
- p.Asn95Asp Multiple submitters Inborn genetic diseases ⚠
- p.Asn95Ser Multiple submitters Inborn genetic diseases ⚠
- p.Asp521Asn Multiple submitters intellectual disability, X-linked 63 ⚠
- p.Cys129Ser Multiple submitters Inborn genetic diseases ⚠
- p.His150Leu Multiple submitters autism spectrum disorder ⚠
- p.His23Arg Multiple submitters Inborn genetic diseases ⚠
- p.Lys271Arg Multiple submitters intellectual disability, X-linked 63 ⚠
- p.Lys388Arg Multiple submitters intellectual disability, X-linked 63 ⚠
- p.Pro404Leu Multiple submitters Inborn genetic diseases ⚠
- p.Pro472Ala Multiple submitters ⚠
- p.Ser501Tyr Multiple submitters Inborn genetic diseases ⚠
- p.Tyr132Cys Multiple submitters Inborn genetic diseases ⚠
- c.1315+1G>T Single submitter
- c.1316-2A>T Single submitter intellectual disability, X-linked 63
- c.1583-7_1583-6del Single submitter
- c.1698-3dup Single submitter intellectual disability, X-linked 63
- c.228+7T>G Single submitter
- c.406+1G>A Single submitter
- c.406+2dup Single submitter
- c.-10G>T Single submitter intellectual disability, X-linked 63 ⚠
- c.-12-104T>G Single submitter ⚠
- c.-12-110T>C Single submitter intellectual disability
- c.-12-2A>G Single submitter ⚠
- c.-12-53C>G Single submitter ⚠
- c.-12-7T>G Single submitter ⚠
- p.Ala103Val Single submitter ⚠
- p.Ala232Val Single submitter ⚠
- p.Ala28Ser Single submitter ⚠
- p.Ala433Gly Single submitter Inborn genetic diseases ⚠
- p.Ala497Val Single submitter ⚠
- p.Ala616Ser Single submitter intellectual disability, X-linked 63 ⚠
- p.Ala647Val Single submitter ⚠
- p.Arg396Gly Single submitter ⚠
- p.Arg396His Single submitter ⚠
- p.Arg475Ser Single submitter ⚠
- p.Arg529Gly Single submitter ⚠
- p.Arg581fs Single submitter
- p.Asn253Ser Single submitter ⚠
- p.Asn343Thr Single submitter intellectual disability, X-linked 63 ⚠
- p.Asn473Asp Single submitter intellectual disability, X-linked 63 ⚠
- p.Asn473Lys Single submitter Inborn genetic diseases ⚠
- p.Asn86Ser Single submitter Inborn genetic diseases ⚠
- p.Asn96Ile Single submitter ⚠
- p.Asp12Gly Single submitter Inborn genetic diseases ⚠
- p.Asp177Gly Single submitter Inborn genetic diseases ⚠
- p.Asp25Asn Single submitter ⚠
- p.Asp597Gly Single submitter ⚠
- p.Gln349Arg Single submitter Inborn genetic diseases ⚠
- p.Gln462Arg Single submitter Inborn genetic diseases ⚠
- p.Gln588His Single submitter Inborn genetic diseases ⚠
- p.Glu156Asp Single submitter intellectual disability, X-linked 63 ⚠
- p.Glu210Gly Single submitter ⚠
- p.Glu350Gly Single submitter Inborn genetic diseases ⚠
- p.Glu494Asp Single submitter ⚠
- p.Gly105Arg Single submitter ⚠
- p.Gly144Ser Single submitter ⚠
- p.Gly15Glu Single submitter ⚠
- p.Gly269Ter Single submitter intellectual disability, X-linked 63
- p.Gly373Arg Single submitter Inborn genetic diseases ⚠
- p.Gly432Asp Single submitter ⚠
- p.Gly465Cys Single submitter ⚠
- p.Gly488= Single submitter
- p.Gly488Arg Single submitter ⚠
- p.Gly539Arg Single submitter ⚠
- p.His23Tyr Single submitter intellectual disability, X-linked 63 ⚠
- p.His658Arg Single submitter ⚠
- p.Ile178Thr Single submitter ⚠
- p.Ile255Leu Single submitter Inborn genetic diseases ⚠
- p.Ile299Val Single submitter ⚠
- p.Ile32Met Single submitter ⚠
- p.Ile32Val Single submitter ⚠
- p.Ile626Val Single submitter Inborn genetic diseases ⚠
- p.Leu160Met Single submitter ⚠
- p.Leu286Val Single submitter ⚠
- p.Leu367Ser Single submitter ⚠
- p.Leu381= Single submitter intellectual disability, X-linked 63
- p.Leu382Ser Single submitter ⚠
- p.Leu61Val Single submitter ⚠
- p.Leu79Phe Single submitter ⚠
- p.Lys109Asn Single submitter ⚠
- p.Lys51Glu Single submitter ⚠
- p.Lys52del Single submitter intellectual disability, X-linked 63
- p.Lys661Gln Single submitter ⚠
- p.Lys75Thr Single submitter ⚠
- p.Met206Val Single submitter ⚠
- p.Met235Thr Single submitter ⚠
- p.Met258Arg Single submitter ⚠
- p.Met330Ile Single submitter ⚠
- p.Met345Thr Single submitter ⚠
- p.Met351fs Single submitter intellectual disability, X-linked 63
- p.Met351Val Single submitter intellectual disability, X-linked 63 ⚠
- p.Met487Val Single submitter ⚠
- p.Met619fs Single submitter
- p.Phe201Cys Single submitter ⚠
- p.Phe49Tyr Single submitter Inborn genetic diseases ⚠
- p.Pro135Ala Single submitter Inborn genetic diseases ⚠
- p.Pro244Leu Single submitter ⚠
- p.Pro304Leu Single submitter ⚠
- p.Pro304Ser Single submitter intellectual disability, X-linked 63 ⚠
- p.Pro334fs Single submitter intellectual disability, X-linked 63
- p.Pro334Gly Single submitter
- p.Pro377Ser Single submitter ⚠
- p.Pro404Gln Single submitter ⚠
- p.Pro627Ser Single submitter ⚠
- p.Pro636Ser Single submitter ⚠
- p.Pro9Ser Single submitter ⚠
- p.Ser16Ile Single submitter ⚠
- p.Ser291Tyr Single submitter ⚠
- p.Ser501Phe Single submitter ⚠
- p.Thr111Asn Single submitter intellectual disability ⚠
- p.Thr22Ile Single submitter ⚠
- p.Thr357Asn Single submitter ⚠
- p.Thr496Ile Single submitter ⚠
- p.Thr594= Single submitter
- p.Trp461Cys Single submitter ⚠
- p.Trp637Leu Single submitter ⚠
- p.Tyr140Cys Single submitter ⚠
- p.Tyr159Phe Single submitter ⚠
- p.Tyr186His Single submitter ⚠
- p.Tyr341Cys Single submitter ⚠
- p.Tyr341Ser Single submitter ⚠
- p.Val576fs Single submitter
- p.Val591Ile Single submitter ⚠
- p.Arg631Ter No assertion criteria ACSL4-related disorder
- p.Asn484His No assertion criteria intellectual disability, X-linked 63 ⚠
- p.Lys40Asn No assertion criteria ACSL4-related disorder ⚠
- p.Thr241Ala No assertion criteria intellectual disability, X-linked 63 ⚠