DARS1 — 237 ClinVar variants
All ClinVar germline DARS1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 107 flagged for review →
5 Pathogenic · 6 Likely pathogenic · 9 Conflicting · 20 Benign · 2 Benign/Likely benign · 83 Likely benign · 112 Uncertain significance
Full DARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 107
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.
-
DARS1 p.Arg460His
Likely pathogenic
Single submitter
hypomyelination with brain stem and spinal cord involvement and leg spasticity
Predictors agree, ClinVar conflicts 3
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
-
DARS1 p.Arg487Cys
Conflicting
Single submitter
hypomyelination with brain stem and spinal cord involvement and leg spasticity
-
DARS1 p.Leu426Ser
Conflicting
Single submitter
hypomyelination with brain stem and spinal cord involvement and leg spasticity
-
DARS1 p.Pro162Ser
Conflicting
Single submitter
hypomyelination with brain stem and spinal cord involvement and leg spasticity
Predictors lean, ClinVar uncertain 63
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
- DARS1 p.Ala429Thr Uncertain significance Multiple submitters
-
DARS1 p.Arg498Gln
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
DARS1 p.Arg63His
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
DARS1 p.Arg81His
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
DARS1 p.Asn233Ser
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
DARS1 p.Ile145Val
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
DARS1 p.Ile224Thr
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
DARS1 p.Met101Leu
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
DARS1 p.Met478Leu
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
DARS1 p.Phe215Ser
Uncertain significance
Multiple submitters
hypomyelination with brain stem and spinal cord involvement and leg spasticity
-
DARS1 p.Ala4Val
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Arg161Trp
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Arg171Gly
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Arg179Ile
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Arg421Gly Uncertain significance Single submitter
- DARS1 p.Arg487His Uncertain significance Single submitter
- DARS1 p.Arg494Cys Uncertain significance Single submitter
- DARS1 p.Asn107Ser Uncertain significance Single submitter
- DARS1 p.Asn243Ser Uncertain significance Single submitter
- DARS1 p.Asn329His Uncertain significance Single submitter
-
DARS1 p.Asp157Gly
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Asp367His
Uncertain significance
Single submitter
hypomyelination with brain stem and spinal cord involvement and leg spasticity
- DARS1 p.Asp417Asn Uncertain significance Single submitter
-
DARS1 p.Asp57Glu
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Cys203Arg Uncertain significance Single submitter
-
DARS1 p.Cys259Tyr
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Cys334Arg Uncertain significance Single submitter
-
DARS1 p.Cys349Tyr
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Cys76Tyr
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Gln11Arg Uncertain significance Single submitter
-
DARS1 p.Gln251Pro
Uncertain significance
Single submitter
hypomyelination with brain stem and spinal cord involvement and leg spasticity
-
DARS1 p.Gln255His
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Gly231Arg
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Gly422Arg
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.His282Pro
Uncertain significance
Single submitter
hypomyelination with brain stem and spinal cord involvement and leg spasticity
-
DARS1 p.His433Arg
Uncertain significance
Single submitter
hypomyelination with brain stem and spinal cord involvement and leg spasticity
- DARS1 p.His67Arg Uncertain significance Single submitter
- DARS1 p.Ile127Thr Uncertain significance Single submitter
-
DARS1 p.Ile291Val
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Ile53Val Uncertain significance Single submitter
-
DARS1 p.Leu246Pro
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Leu317Phe Uncertain significance Single submitter
- DARS1 p.Lys315Arg Uncertain significance Single submitter
-
DARS1 p.Lys338Thr
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Lys497Thr
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Met256Lys Uncertain significance Single submitter
-
DARS1 p.Met310Val
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Met354Thr
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Met404Val Uncertain significance Single submitter
-
DARS1 p.Phe266Leu
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Phe286Leu Uncertain significance Single submitter
-
DARS1 p.Pro162Ala
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Pro405Ser
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Pro496Ala Uncertain significance Single submitter
- DARS1 p.Ser228Gly Uncertain significance Single submitter
-
DARS1 p.Ser277Cys
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Ser277Phe
Uncertain significance
Single submitter
hypomyelination with brain stem and spinal cord involvement and leg spasticity
-
DARS1 p.Thr191Ala
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Thr323Ser
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Tyr29Asp Uncertain significance Single submitter
- DARS1 p.Val174Leu Uncertain significance Single submitter
-
DARS1 p.Val184Gly
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Val195Ile Uncertain significance Single submitter
Predictors split 40
The independent predictors disagree with each other — read with care.
-
DARS1 p.Glu357Lys
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
DARS1 p.Gly170Arg
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
DARS1 p.Gly359Glu
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
DARS1 p.His138Arg
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
DARS1 p.Ala92Val
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Arg151Cys
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Arg151His
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Arg197Cys
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Arg197His Conflicting Single submitter
-
DARS1 p.Arg207Gln
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Arg43Gln
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Asn278Tyr Uncertain significance Single submitter
-
DARS1 p.Gln436Arg
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Glu169Lys
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Glu208Gln Uncertain significance Single submitter
- DARS1 p.Glu27Lys Uncertain significance Single submitter
- DARS1 p.Glu335Lys Uncertain significance Single submitter
- DARS1 p.Glu341Asp Uncertain significance Single submitter
-
DARS1 p.Glu361Lys
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Gly363Glu Conflicting Single submitter
- DARS1 p.His300Asp Uncertain significance Single submitter
-
DARS1 p.Ile113Val
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Ile223Val Uncertain significance Single submitter
-
DARS1 p.Leu481Val
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Lys141Glu
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Met303Thr
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Met303Val
Likely benign
Single submitter
Inborn genetic diseases
- DARS1 p.Pro342Thr Uncertain significance Single submitter
-
DARS1 p.Pro435Ser
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Pro464Leu Conflicting Single submitter
-
DARS1 p.Ser146Cys
Uncertain significance
Single submitter
Inborn genetic diseases
- DARS1 p.Ser200Cys Uncertain significance Single submitter
-
DARS1 p.Ser69Gly
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Thr191Ser
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Thr386Ala
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Thr439Ala
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Thr439Arg
Uncertain significance
Single submitter
Inborn genetic diseases
-
DARS1 p.Val135Ile
Conflicting
Single submitter
hypomyelination with brain stem and spinal cord involvement and leg spasticity
-
DARS1 p.Val360Ile
Likely benign
Single submitter
Inborn genetic diseases
- DARS1 p.Val476Ile Uncertain significance Single submitter
All DARS1 variants
Pathogenic 5
- p.Ala274Gly Single submitter
- p.Ala274Val No assertion criteria hypomyelination with brain stem and spinal cord involvement and leg spasticity
- p.Asp367Tyr No assertion criteria hypomyelination with brain stem and spinal cord involvement and leg spasticity
- p.His280Leu No assertion criteria hypomyelination with brain stem and spinal cord involvement and leg spasticity
- p.Met256Leu No assertion criteria hypomyelination with brain stem and spinal cord involvement and leg spasticity
Likely pathogenic 6
- p.Arg460His Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity ⚠
- p.Arg494Gly Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity
- p.Arg494His Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity
- p.Cys130Ser Single submitter Abnormal brain morphology
- p.Gly377Arg Single submitter
- p.Tyr245Ter Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity
Conflicting classifications of pathogenicity 9
- c.1150-5T>G Single submitter
- c.125-18C>T Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity
- p.Arg197His Single submitter ⚠
- p.Arg487Cys Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity ⚠
- p.Gly363Glu Single submitter ⚠
- p.Leu426Ser Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity ⚠
- p.Pro162Ser Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity ⚠
- p.Pro464Leu Single submitter ⚠
- p.Val135Ile Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity ⚠
Benign 20
- c.124+67A>G Multiple submitters
- c.1342+14A>G Multiple submitters
- c.1414+18C>T Multiple submitters
- c.218-105T>C Multiple submitters
- c.423+21A>G Multiple submitters
- c.504+123C>T Multiple submitters
- c.505-13T>C Multiple submitters hypomyelination with brain stem and spinal cord involvement and leg spasticity
- c.505-3del Multiple submitters hypomyelination with brain stem and spinal cord involvement and leg spasticity
- c.66+34A>G Multiple submitters
- c.677-46T>C Multiple submitters
- c.959+104C>A Multiple submitters
- c.960-86T>C Multiple submitters
- c.-100T>C Multiple submitters
- c.-105C>G Multiple submitters
- c.-42C>G Multiple submitters
- p.Ile268Val Multiple submitters
- p.Leu473= Multiple submitters
- c.125-17G>A Single submitter
- c.67-6_67-5del Single submitter
- c.959+65dup Single submitter
Benign/Likely benign 2
- c.321-19G>C Multiple submitters
- p.Ala274= Multiple submitters
Likely benign 83
- c.1230+17T>C Multiple submitters
- c.124+15G>T Multiple submitters
- c.504+34G>A Multiple submitters
- c.505-18_505-6del Multiple submitters
- c.67-149T>G Multiple submitters
- p.4AS[3] Multiple submitters
- p.Gln251= Multiple submitters
- p.Gln436= Multiple submitters
- p.Leu156= Multiple submitters
- p.Phe286= Multiple submitters
- p.Ser190= Multiple submitters
- p.Thr386= Multiple submitters
- c.1107-13G>A Single submitter
- c.1149+15A>G Single submitter
- c.1149+7C>A Single submitter
- c.1149+7C>G Single submitter
- c.1230+13G>A Single submitter
- c.1230+8A>G Single submitter
- c.125-10G>A Single submitter
- c.125-18C>G Single submitter
- c.125-6T>C Single submitter
- c.1342+12A>G Single submitter
- c.1342+19T>C Single submitter
- c.1342+9_1342+13del Single submitter
- c.1343-7T>A Single submitter
- c.1343-7T>C Single submitter
- c.1414+19T>G Single submitter
- c.1415-11del Single submitter
- c.217+9G>C Single submitter
- c.218-20G>T Single submitter
- c.218-22_218-19del Single submitter
- c.218-9C>G Single submitter
- c.320+12A>G Single submitter
- c.320+8A>G Single submitter
- c.423+15A>C Single submitter
- c.423+17T>C Single submitter
- c.423+4A>T Single submitter
- c.424-14T>C Single submitter
- c.504+17T>C Single submitter
- c.505-15_505-14insC Single submitter
- c.505-18_505-14del Single submitter
- c.505-3dup Single submitter
- c.505-4_505-3del Single submitter
- c.505-4T>C Single submitter
- c.564+16T>G Single submitter
- c.565-12A>G Single submitter
- c.565-13T>C Single submitter
- c.565-6T>C Single submitter
- c.66+18C>T Single submitter
- c.67-17A>G Single submitter
- c.676+125del Single submitter
- c.812-4A>G Single submitter
- c.959+17G>A Single submitter
- c.960-15T>C Single submitter
- p.Ala397= Single submitter
- p.Ala92= Single submitter
- p.Arg28= Single submitter
- p.Arg460= Single submitter
- p.Asn329= Single submitter
- p.Asn86= Single submitter
- p.Asp19= Single submitter
- p.Gln11= Single submitter
- p.Gln326= Single submitter
- p.Glu169= Single submitter
- p.Glu361= Single submitter
- p.Glu373= Single submitter
- p.Gly201= Single submitter
- p.His300= Single submitter
- p.Ile53= Single submitter
- p.Leu152= Single submitter
- p.Leu368= Single submitter
- p.Leu375= Single submitter
- p.Lys122= Single submitter
- p.Lys13= Single submitter
- p.Lys254= Single submitter
- p.Met303Val Single submitter Inborn genetic diseases ⚠
- p.Ser458= Single submitter
- p.Tyr29= Single submitter
- p.Val119= Single submitter
- p.Val360= Single submitter
- p.Val360Ile Single submitter Inborn genetic diseases ⚠
- c.1107-10T>C No assertion criteria DARS1-related disorder
- c.505-2dup No assertion criteria DARS1-related disorder
Uncertain significance 112
- p.Ala429Thr Multiple submitters ⚠
- p.Arg498Gln Multiple submitters Inborn genetic diseases ⚠
- p.Arg63His Multiple submitters Inborn genetic diseases ⚠
- p.Arg81His Multiple submitters Inborn genetic diseases ⚠
- p.Asn233Ser Multiple submitters Inborn genetic diseases ⚠
- p.Glu357Lys Multiple submitters Inborn genetic diseases ⚠
- p.Gly170Arg Multiple submitters Inborn genetic diseases ⚠
- p.Gly359Glu Multiple submitters Inborn genetic diseases ⚠
- p.His138Arg Multiple submitters Inborn genetic diseases ⚠
- p.Ile145Val Multiple submitters Inborn genetic diseases ⚠
- p.Ile224Thr Multiple submitters Inborn genetic diseases ⚠
- p.Met101Leu Multiple submitters Inborn genetic diseases ⚠
- p.Met478Leu Multiple submitters Inborn genetic diseases ⚠
- p.Phe215Ser Multiple submitters hypomyelination with brain stem and spinal cord involvement and leg spasticity ⚠
- c.1149+3A>C Single submitter
- c.1149+8T>G Single submitter
- c.1150-10_1150-8del Single submitter
- c.1230+1G>A Single submitter
- c.1231-455A>G Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity
- c.504+2T>G Single submitter
- c.564+2264G>A Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity
- c.676+6C>T Single submitter Inborn genetic diseases
- c.959+3A>T Single submitter
- p.Ala4Val Single submitter Inborn genetic diseases ⚠
- p.Ala92Val Single submitter Inborn genetic diseases ⚠
- p.Arg151Cys Single submitter Inborn genetic diseases ⚠
- p.Arg151His Single submitter Inborn genetic diseases ⚠
- p.Arg161Trp Single submitter Inborn genetic diseases ⚠
- p.Arg171Gly Single submitter Inborn genetic diseases ⚠
- p.Arg179Ile Single submitter Inborn genetic diseases ⚠
- p.Arg197Cys Single submitter Inborn genetic diseases ⚠
- p.Arg207Gln Single submitter Inborn genetic diseases ⚠
- p.Arg421Gly Single submitter ⚠
- p.Arg43Gln Single submitter Inborn genetic diseases ⚠
- p.Arg43Ter Single submitter
- p.Arg441fs Single submitter
- p.Arg487His Single submitter ⚠
- p.Arg494Cys Single submitter ⚠
- p.Arg498Ter Single submitter
- p.Asn107Ser Single submitter ⚠
- p.Asn243Ser Single submitter ⚠
- p.Asn278Tyr Single submitter ⚠
- p.Asn329His Single submitter ⚠
- p.Asp157Gly Single submitter Inborn genetic diseases ⚠
- p.Asp367His Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity ⚠
- p.Asp417Asn Single submitter ⚠
- p.Asp57Glu Single submitter Inborn genetic diseases ⚠
- p.Cys203Arg Single submitter ⚠
- p.Cys259Tyr Single submitter Inborn genetic diseases ⚠
- p.Cys334Arg Single submitter ⚠
- p.Cys349Tyr Single submitter Inborn genetic diseases ⚠
- p.Cys76Tyr Single submitter Inborn genetic diseases ⚠
- p.Gln11Arg Single submitter ⚠
- p.Gln155Ter Single submitter
- p.Gln251Pro Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity ⚠
- p.Gln255His Single submitter Inborn genetic diseases ⚠
- p.Gln38Ter Single submitter
- p.Gln430Ter Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity
- p.Gln436Arg Single submitter Inborn genetic diseases ⚠
- p.Glu169Lys Single submitter Inborn genetic diseases ⚠
- p.Glu208Gln Single submitter ⚠
- p.Glu27Lys Single submitter ⚠
- p.Glu335Lys Single submitter ⚠
- p.Glu341Asp Single submitter ⚠
- p.Glu361Lys Single submitter Inborn genetic diseases ⚠
- p.Gly231Arg Single submitter Inborn genetic diseases ⚠
- p.Gly422Arg Single submitter Inborn genetic diseases ⚠
- p.His282Pro Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity ⚠
- p.His300Asp Single submitter ⚠
- p.His433Arg Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity ⚠
- p.His67Arg Single submitter ⚠
- p.Ile113Val Single submitter Inborn genetic diseases ⚠
- p.Ile127Thr Single submitter ⚠
- p.Ile223Val Single submitter ⚠
- p.Ile291Val Single submitter Inborn genetic diseases ⚠
- p.Ile53Val Single submitter ⚠
- p.Leu246Pro Single submitter Inborn genetic diseases ⚠
- p.Leu317Phe Single submitter ⚠
- p.Leu481Val Single submitter Inborn genetic diseases ⚠
- p.Lys141Glu Single submitter Inborn genetic diseases ⚠
- p.Lys315Arg Single submitter ⚠
- p.Lys338Thr Single submitter Inborn genetic diseases ⚠
- p.Lys497Thr Single submitter Inborn genetic diseases ⚠
- p.Met256Lys Single submitter ⚠
- p.Met303Thr Single submitter Inborn genetic diseases ⚠
- p.Met310Val Single submitter Inborn genetic diseases ⚠
- p.Met354Thr Single submitter Inborn genetic diseases ⚠
- p.Met404Val Single submitter ⚠
- p.Phe266Leu Single submitter Inborn genetic diseases ⚠
- p.Phe286Leu Single submitter ⚠
- p.Pro162Ala Single submitter Inborn genetic diseases ⚠
- p.Pro342Thr Single submitter ⚠
- p.Pro405Ser Single submitter Inborn genetic diseases ⚠
- p.Pro435Ser Single submitter Inborn genetic diseases ⚠
- p.Pro496Ala Single submitter ⚠
- p.Ser146Cys Single submitter Inborn genetic diseases ⚠
- p.Ser200Cys Single submitter ⚠
- p.Ser228Gly Single submitter ⚠
- p.Ser277Cys Single submitter Inborn genetic diseases ⚠
- p.Ser277Phe Single submitter hypomyelination with brain stem and spinal cord involvement and leg spasticity ⚠
- p.Ser69Gly Single submitter Inborn genetic diseases ⚠
- p.Thr191Ala Single submitter Inborn genetic diseases ⚠
- p.Thr191Ser Single submitter Inborn genetic diseases ⚠
- p.Thr323Ser Single submitter Inborn genetic diseases ⚠
- p.Thr386Ala Single submitter Inborn genetic diseases ⚠
- p.Thr439Ala Single submitter Inborn genetic diseases ⚠
- p.Thr439Arg Single submitter Inborn genetic diseases ⚠
- p.Tyr29Asp Single submitter ⚠
- p.Val174Leu Single submitter ⚠
- p.Val184Gly Single submitter Inborn genetic diseases ⚠
- p.Val195Ile Single submitter ⚠
- p.Val476Ile Single submitter ⚠