SIGMAR1 — 173 ClinVar variants
All ClinVar germline SIGMAR1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 64 flagged for review →
9 Pathogenic · 2 Pathogenic/Likely pathogenic · 10 Likely pathogenic · 3 Conflicting · 7 Benign · 1 Benign/Likely benign · 69 Likely benign · 72 Uncertain significance
Full SIGMAR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 64
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 agree, ClinVar conflicts 2
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
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SIGMAR1 p.Arg211Gln
Conflicting
Single submitter
Inborn genetic diseases
-
SIGMAR1 p.Gly155Arg
Conflicting
Single submitter
Inborn genetic diseases
Predictors lean, ClinVar uncertain 42
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
-
SIGMAR1 p.Asn85Ser
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
SIGMAR1 p.Gly115Val
Uncertain significance
Multiple submitters
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Gly155Trp
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
SIGMAR1 p.Gly87Arg
Uncertain significance
Multiple submitters
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Leu100Val
Uncertain significance
Multiple submitters
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Leu182Pro
Uncertain significance
Multiple submitters
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Leu199Phe
Uncertain significance
Multiple submitters
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Ser192Asn
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
SIGMAR1 p.Thr151Met
Uncertain significance
Multiple submitters
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Thr202Ile
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
SIGMAR1 p.Val177Ile
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
SIGMAR1 p.Ala159Val
Uncertain significance
Single submitter
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Ala183Pro
Uncertain significance
Single submitter
Inborn genetic diseases
-
SIGMAR1 p.Ala98Ser
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
- SIGMAR1 p.Arg175Leu Uncertain significance Single submitter
-
SIGMAR1 p.Arg175Trp
Uncertain significance
Single submitter
autosomal recessive distal spinal muscular atrophy 2
- SIGMAR1 p.Arg204Cys Uncertain significance Single submitter
-
SIGMAR1 p.Arg208Gln
Uncertain significance
Single submitter
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Arg208Pro
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Arg211Trp
Uncertain significance
Single submitter
autosomal recessive distal spinal muscular atrophy 2
- SIGMAR1 p.Arg66Trp Uncertain significance Single submitter
- SIGMAR1 p.Arg67Gln Uncertain significance Single submitter
-
SIGMAR1 p.Asp188Asn
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Gln24His
Uncertain significance
Single submitter
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Gly131Ser
Uncertain significance
Single submitter
autosomal recessive distal spinal muscular atrophy 2
- SIGMAR1 p.Gly139Val Uncertain significance Single submitter
-
SIGMAR1 p.Gly149Glu
Uncertain significance
Single submitter
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Gly51Glu
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
- SIGMAR1 p.Leu214Val Uncertain significance Single submitter
-
SIGMAR1 p.Leu218Phe
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
- SIGMAR1 p.Met90Ile Uncertain significance Single submitter
-
SIGMAR1 p.Met93Ile
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Phe83Leu
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Pro166Ser
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Pro223Ala
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Ser205Phe
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Thr127Ile
Uncertain significance
Single submitter
Inborn genetic diseases
-
SIGMAR1 p.Thr198Ile
Uncertain significance
Single submitter
Inborn genetic diseases
-
SIGMAR1 p.Tyr103Cys
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Tyr120Cys
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Tyr206Ser
Uncertain significance
Single submitter
Inborn genetic diseases
-
SIGMAR1 p.Val177Ala
Uncertain significance
Single submitter
autosomal recessive distal spinal muscular atrophy 2
Predictors split 20
The independent predictors disagree with each other — read with care.
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SIGMAR1 p.Ala185Pro
Uncertain significance
Multiple submitters
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Ala185Val
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
SIGMAR1 p.Arg175Gln
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
SIGMAR1 p.Glu102Gln
Pathogenic
Multiple submitters
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Glu150Lys
Likely pathogenic
Multiple submitters
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Gly174Ser
Uncertain significance
Multiple submitters
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Gly87Ser
Uncertain significance
Multiple submitters
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Pro70Arg
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
SIGMAR1 p.Ala161Asp
Uncertain significance
Single submitter
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Arg119His
Conflicting
Single submitter
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Cys94Tyr
Uncertain significance
Single submitter
Inborn genetic diseases
-
SIGMAR1 p.Gly174Val
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
- SIGMAR1 p.Gly209Asp Uncertain significance Single submitter
-
SIGMAR1 p.Met170Ile
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Phe133Cys
Uncertain significance
Single submitter
Inborn genetic diseases
-
SIGMAR1 p.Phe191Leu
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Val104Ala
Uncertain significance
Single submitter
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Val171Leu
Uncertain significance
Single submitter
autosomal recessive distal spinal muscular atrophy 2
-
SIGMAR1 p.Val73Ala
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
-
SIGMAR1 p.Val84Leu
Uncertain significance
Single submitter
amyotrophic lateral sclerosis type 16
All SIGMAR1 variants
Pathogenic 9
- p.Glu102Gln Multiple submitters autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Leu95fs Multiple submitters autosomal recessive distal spinal muscular atrophy 2
- c.445+1G>A Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Gln135Ter Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Gln80Ter Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Ser125Ter Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Trp164Ter Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Val153fs Single submitter amyotrophic lateral sclerosis type 16
- p.Val73fs Single submitter autosomal recessive distal spinal muscular atrophy 2
Pathogenic/Likely pathogenic 2
- p.Arg7fs Multiple submitters Inborn genetic diseases
- p.Leu65Gln Multiple submitters amyotrophic lateral sclerosis type 16
Likely pathogenic 10
- p.Asp188fs Multiple submitters autosomal recessive distal spinal muscular atrophy 2
- p.Glu150Lys Multiple submitters amyotrophic lateral sclerosis type 16 ⚠
- c.152-2A>T Single submitter amyotrophic lateral sclerosis type 16
- c.353-2A>G Single submitter amyotrophic lateral sclerosis type 16
- c.446-25_*40del Single submitter amyotrophic lateral sclerosis type 16
- c.446-2A>C Single submitter
- p.Glu213Lys Single submitter amyotrophic lateral sclerosis type 16
- p.Phe37fs Single submitter amyotrophic lateral sclerosis type 16
- p.Ter224Trp Single submitter amyotrophic lateral sclerosis type 16
- p.Thr151Ala Single submitter amyotrophic lateral sclerosis type 16
Conflicting classifications of pathogenicity 3
- p.Arg119His Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Arg211Gln Single submitter Inborn genetic diseases ⚠
- p.Gly155Arg Single submitter Inborn genetic diseases ⚠
Benign 7
- c.445+171C>G Multiple submitters
- c.446-44C>G Multiple submitters
- c.*31A>G Multiple submitters autosomal recessive distal spinal muscular atrophy 2
- p.Gln80= Multiple submitters autosomal recessive distal spinal muscular atrophy 2
- p.Phe184= Multiple submitters autosomal recessive distal spinal muscular atrophy 2
- c.151+15G>A Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.446-257G>A Single submitter
Benign/Likely benign 1
- p.Arg208Trp Multiple submitters autosomal recessive distal spinal muscular atrophy 2
Likely benign 69
- p.Ala122= Multiple submitters autosomal recessive distal spinal muscular atrophy 2
- p.Glu213= Multiple submitters autosomal recessive distal spinal muscular atrophy 2
- c.151+16G>A Single submitter amyotrophic lateral sclerosis type 16
- c.151+16G>C Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.151+19G>A Single submitter amyotrophic lateral sclerosis type 16
- c.152-15C>T Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.152-16C>T Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.152-4C>A Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.152-6C>T Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.152-7C>T Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.352+10A>G Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.352+12C>T Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.352+16G>C Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.353-13G>A Single submitter amyotrophic lateral sclerosis type 16
- c.353-9G>C Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.445+13G>A Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.445+14C>T Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.445+17T>A Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.445+7A>G Single submitter
- c.446-10T>C Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.446-16G>A Single submitter amyotrophic lateral sclerosis type 16
- c.446-19G>A Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.446-5C>G Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.446-7C>G Single submitter amyotrophic lateral sclerosis type 16
- c.446-7C>T Single submitter autosomal recessive distal spinal muscular atrophy 2
- c.*27G>A Single submitter
- c.*42G>T Single submitter
- p.Ala187= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Ala57= Single submitter amyotrophic lateral sclerosis type 16
- p.Ala98= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Arg175= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Arg211= Single submitter amyotrophic lateral sclerosis type 16
- p.Arg66= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Asn85= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Glu123= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Gly176= Single submitter amyotrophic lateral sclerosis type 16
- p.Gly209= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Gly220= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Gly51= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Gly87= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.His116= Single submitter amyotrophic lateral sclerosis type 16
- p.His154= Single submitter amyotrophic lateral sclerosis type 16
- p.His69= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.His72= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.His97= Single submitter amyotrophic lateral sclerosis type 16
- p.Ile124= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Leu100= Single submitter amyotrophic lateral sclerosis type 16
- p.Leu111= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Leu182= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Leu214= Single submitter amyotrophic lateral sclerosis type 16
- p.Leu218= Single submitter
- p.Leu65= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Leu68= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Leu79= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Leu96= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Phe200= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Ser101= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Ser113= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Ser125= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Ser59= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Ser99= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Thr151= Single submitter amyotrophic lateral sclerosis type 16
- p.Thr181= Single submitter amyotrophic lateral sclerosis type 16
- p.Thr189= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Thr32= Single submitter amyotrophic lateral sclerosis type 16
- p.Tyr103= Single submitter amyotrophic lateral sclerosis type 16
- p.Tyr173= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Tyr206= Single submitter amyotrophic lateral sclerosis type 16
- p.Val152= Single submitter amyotrophic lateral sclerosis type 16
Uncertain significance 72
- p.Ala185Pro Multiple submitters autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Ala185Val Multiple submitters Inborn genetic diseases ⚠
- p.Arg175Gln Multiple submitters Inborn genetic diseases ⚠
- p.Asn85Ser Multiple submitters Inborn genetic diseases ⚠
- p.Gly115Val Multiple submitters autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Gly155Trp Multiple submitters Inborn genetic diseases ⚠
- p.Gly174Ser Multiple submitters autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Gly87Arg Multiple submitters autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Gly87Ser Multiple submitters autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Leu100Val Multiple submitters amyotrophic lateral sclerosis type 16 ⚠
- p.Leu182Pro Multiple submitters amyotrophic lateral sclerosis type 16 ⚠
- p.Leu199Phe Multiple submitters autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Pro70Arg Multiple submitters Inborn genetic diseases ⚠
- p.Ser192Asn Multiple submitters Inborn genetic diseases ⚠
- p.Thr151Met Multiple submitters autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Thr202Ile Multiple submitters Inborn genetic diseases ⚠
- p.Val177Ile Multiple submitters Inborn genetic diseases ⚠
- c.*51G>T Single submitter amyotrophic lateral sclerosis type 16
- c.*9G>C Single submitter
- p.Ala159Val Single submitter autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Ala161Asp Single submitter autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Ala183Pro Single submitter Inborn genetic diseases ⚠
- p.Ala185Thr Single submitter amyotrophic lateral sclerosis type 16
- p.Ala57Gly Single submitter amyotrophic lateral sclerosis type 16
- p.Ala98Ser Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Arg175Leu Single submitter ⚠
- p.Arg175Trp Single submitter autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Arg204Cys Single submitter ⚠
- p.Arg208Gln Single submitter autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Arg208Pro Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Arg211Trp Single submitter autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Arg66Trp Single submitter ⚠
- p.Arg67Gln Single submitter ⚠
- p.Asp188Asn Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Cys94Tyr Single submitter Inborn genetic diseases ⚠
- p.Gln24His Single submitter autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Gly131Ser Single submitter autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Gly139Val Single submitter ⚠
- p.Gly149Glu Single submitter autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Gly157Ala Single submitter amyotrophic lateral sclerosis type 16
- p.Gly174Val Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Gly209Asp Single submitter ⚠
- p.Gly51Glu Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Gly71Ala Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Leu214Val Single submitter ⚠
- p.Leu218Phe Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Met170Ile Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Met90Ile Single submitter ⚠
- p.Met93Ile Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Phe133Cys Single submitter Inborn genetic diseases ⚠
- p.Phe184_Ala187del Single submitter amyotrophic lateral sclerosis type 16
- p.Phe191Leu Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Phe219fs Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Phe58del Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Phe83Leu Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Pro166Ser Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Pro223Ala Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Pro70Ser Single submitter amyotrophic lateral sclerosis type 16
- p.Ser113Cys Single submitter amyotrophic lateral sclerosis type 16
- p.Ser117= Single submitter autosomal recessive distal spinal muscular atrophy 2
- p.Ser205Phe Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Thr127Ile Single submitter Inborn genetic diseases ⚠
- p.Thr198Ile Single submitter Inborn genetic diseases ⚠
- p.Tyr103Cys Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Tyr120Cys Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Tyr206Ser Single submitter Inborn genetic diseases ⚠
- p.Val104Ala Single submitter autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Val171Leu Single submitter autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Val177Ala Single submitter autosomal recessive distal spinal muscular atrophy 2 ⚠
- p.Val73Ala Single submitter amyotrophic lateral sclerosis type 16 ⚠
- p.Val82Met Single submitter Inborn genetic diseases
- p.Val84Leu Single submitter amyotrophic lateral sclerosis type 16 ⚠