SPR — 203 ClinVar variants
All ClinVar germline SPR variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 67 flagged for review →
19 Pathogenic · 3 Pathogenic/Likely pathogenic · 6 Likely pathogenic · 12 Conflicting · 6 Benign · 74 Likely benign · 83 Uncertain significance
Full SPR gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 67
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 6
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
-
SPR p.Ala175Asp
Conflicting
Single submitter
dopa-responsive dystonia due to sepiapterin reductase deficiency
-
SPR p.Arg210Trp
Conflicting
Single submitter
dystonic disorder
-
SPR p.Arg88Trp
Conflicting
Single submitter
Inborn genetic diseases
-
SPR p.Asn127Lys
Conflicting
Single submitter
dopa-responsive dystonia due to sepiapterin reductase deficiency
-
SPR p.Glu249Lys
Conflicting
Single submitter
dystonic disorder
-
SPR p.Val236Met
Conflicting
Single submitter
Inborn genetic diseases
Predictors lean, ClinVar uncertain 45
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
-
SPR p.Ala168Thr
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
SPR p.Arg219Gln
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
SPR p.Asn122Ser
Uncertain significance
Multiple submitters
dystonic disorder
-
SPR p.Asn127Ser
Uncertain significance
Multiple submitters
dystonic disorder
-
SPR p.Gly110Arg
Uncertain significance
Multiple submitters
dopa-responsive dystonia due to sepiapterin reductase deficiency
-
SPR p.Met218Ile
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
SPR p.Pro89Leu
Uncertain significance
Multiple submitters
dopa-responsive dystonia due to sepiapterin reductase deficiency
-
SPR p.Ser103Cys
Uncertain significance
Multiple submitters
dystonic disorder
-
SPR p.Val112Leu
Uncertain significance
Multiple submitters
dystonic disorder
-
SPR p.Ala125Thr
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Ala175Thr
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Ala82Thr
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Arg177Gly
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Arg177His
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Arg88Gln
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Asn154Ile
Uncertain significance
Single submitter
Inborn genetic diseases
-
SPR p.Asp204His
Uncertain significance
Single submitter
dopa-responsive dystonia due to sepiapterin reductase deficiency
-
SPR p.Asp215Asn
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Asp257His
Uncertain significance
Single submitter
dystonic disorder
- SPR p.Cys171Arg Uncertain significance Single submitter
-
SPR p.Gln119Pro
Uncertain significance
Single submitter
dystonic disorder
- SPR p.Gly105Arg Uncertain significance Single submitter
-
SPR p.Gly166Asp
Uncertain significance
Single submitter
dopa-responsive dystonia due to sepiapterin reductase deficiency
-
SPR p.Gly199Arg
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Gly253Arg
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Leu104Phe
Uncertain significance
Single submitter
Inborn genetic diseases
-
SPR p.Leu104Pro
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Leu158Phe
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Leu186Val
Uncertain significance
Single submitter
dopa-responsive dystonia due to sepiapterin reductase deficiency
-
SPR p.Leu83Pro
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Leu95Val
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Lys165Gln
Uncertain significance
Single submitter
Inborn genetic diseases
-
SPR p.Lys261Arg
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Pro146Thr
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Pro200Ser
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Pro87Arg
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Pro87Thr
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Ser103Pro
Uncertain significance
Single submitter
dopa-responsive dystonia due to sepiapterin reductase deficiency
-
SPR p.Thr129Ile
Uncertain significance
Single submitter
Inborn genetic diseases
-
SPR p.Tyr123Cys
Uncertain significance
Single submitter
dystonic disorder
- SPR p.Val152Ala Uncertain significance Single submitter
-
SPR p.Val152Met
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Val236Leu
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Leu225Met
Uncertain significance
No assertion criteria
SPR-related disorder
-
SPR p.Trp124Arg
Uncertain significance
No assertion criteria
dopa-responsive dystonia due to sepiapterin reductase deficiency
Predictors split 16
The independent predictors disagree with each other — read with care.
-
SPR p.Arg210Gln
Uncertain significance
Multiple submitters
dystonic disorder
-
SPR p.Arg65Trp
Uncertain significance
Multiple submitters
dystonic disorder
-
SPR p.Met179Thr
Uncertain significance
Multiple submitters
dopa-responsive dystonia due to sepiapterin reductase deficiency
-
SPR p.Val256Met
Uncertain significance
Multiple submitters
dystonic disorder
-
SPR p.Cys133Phe
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Gly166Cys
Uncertain significance
Single submitter
dystonic disorder
- SPR p.Leu158Val Uncertain significance Single submitter
-
SPR p.Leu161Arg
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Leu86Phe
Uncertain significance
Single submitter
dopa-responsive dystonia due to sepiapterin reductase deficiency
-
SPR p.Pro143Ala
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Pro143Arg
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Pro143Leu
Uncertain significance
Single submitter
Inborn genetic diseases
- SPR p.Pro189Leu Uncertain significance Single submitter
-
SPR p.Pro89Arg
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Ser136Cys
Uncertain significance
Single submitter
dystonic disorder
-
SPR p.Val36Met
Uncertain significance
Single submitter
dopa-responsive dystonia due to sepiapterin reductase deficiency
All SPR variants
Pathogenic 19
- p.Arg150Gly Multiple submitters dystonic disorder
- p.Arg219Ter Multiple submitters SPR-related disorder
- p.Gln182Ter Multiple submitters dystonic disorder
- p.Gln239Ter Multiple submitters dystonic disorder
- p.Lys251Ter Multiple submitters SPR-related disorder
- c.304+2_304+13del Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- c.305-2A>G Single submitter intellectual disability
- c.596-2A>G Single submitter dystonic disorder
- c.596del Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Arg88fs Single submitter dystonic disorder
- p.Gln206fs Single submitter dystonic disorder
- p.Gln207Ter Single submitter dystonic disorder
- p.Gln93Ter Single submitter dystonic disorder
- p.Tyr123Ter Single submitter
- p.Tyr196Cys Single submitter Inborn genetic diseases
- p.Gln119Ter No assertion criteria dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Gly102Cys No assertion criteria dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Pro163Leu No assertion criteria dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Thr151fs No assertion criteria dopa-responsive dystonia due to sepiapterin reductase deficiency
Pathogenic/Likely pathogenic 3
- c.596-2_602del Multiple submitters dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Leu222fs Multiple submitters SPR-related disorder
- p.Lys230Ter Multiple submitters dystonic disorder
Likely pathogenic 6
- p.Cys171Tyr Multiple submitters dystonic disorder
- p.Met1Leu Multiple submitters dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Glu187Gly Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Gly173Ter Single submitter
- p.Ter262ProextTer? Single submitter
- p.Glu211fs No assertion criteria dopa-responsive dystonia due to sepiapterin reductase deficiency
Conflicting classifications of pathogenicity 12
- c.305-12T>C Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- c.595+7G>A Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Ala175Asp Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency ⚠
- p.Arg210Trp Single submitter dystonic disorder ⚠
- p.Arg88Trp Single submitter Inborn genetic diseases ⚠
- p.Asn127Lys Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency ⚠
- p.Asp248= Single submitter dystonic disorder
- p.Gln162= Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Gln206Ter Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Glu249Lys Single submitter dystonic disorder ⚠
- p.Tyr123= Single submitter dystonic disorder
- p.Val236Met Single submitter Inborn genetic diseases ⚠
Benign 6
- c.595+32C>G Multiple submitters
- p.Ter262= Multiple submitters dystonic disorder
- c.304+223T>G Single submitter
- c.305-126C>A Single submitter
- c.595+264G>A Single submitter
- c.*432G>A Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
Likely benign 74
- p.Thr13= Multiple submitters dystonic disorder
- c.304+10C>T Single submitter dystonic disorder
- c.304+11G>A Single submitter dystonic disorder
- c.304+13G>A Single submitter dystonic disorder
- c.304+13G>T Single submitter dystonic disorder
- c.304+16T>C Single submitter dystonic disorder
- c.304+18del Single submitter dystonic disorder
- c.305-14G>A Single submitter dystonic disorder
- c.305-17A>G Single submitter dystonic disorder
- c.305-18T>C Single submitter dystonic disorder
- c.305-18T>G Single submitter dystonic disorder
- c.305-19C>T Single submitter dystonic disorder
- c.595+10A>G Single submitter dystonic disorder
- c.595+19C>G Single submitter dystonic disorder
- c.595+19C>T Single submitter dystonic disorder
- c.595+20G>A Single submitter dystonic disorder
- c.596-16C>T Single submitter dystonic disorder
- c.596-20G>A Single submitter dystonic disorder
- c.596-5T>G Single submitter dystonic disorder
- c.596-6C>T Single submitter dystonic disorder
- c.596-9A>G Single submitter dystonic disorder
- p.Ala168= Single submitter dystonic disorder
- p.Ala185= Single submitter dystonic disorder
- p.Ala197= Single submitter dystonic disorder
- p.Ala254= Single submitter dystonic disorder
- p.Arg219= Single submitter dystonic disorder
- p.Arg84= Single submitter dystonic disorder
- p.Arg88= Single submitter dystonic disorder
- p.Arg94= Single submitter dystonic disorder
- p.Asn190= Single submitter dystonic disorder
- p.Asn99= Single submitter dystonic disorder
- p.Asp233= Single submitter dystonic disorder
- p.Glu211= Single submitter dystonic disorder
- p.Gly102= Single submitter dystonic disorder
- p.Gly105= Single submitter dystonic disorder
- p.Gly199= Single submitter
- p.Gly221= Single submitter dystonic disorder
- p.Gly229= Single submitter dystonic disorder
- p.Gly81= Single submitter dystonic disorder
- p.Gly91= Single submitter dystonic disorder
- p.His255= Single submitter dystonic disorder
- p.Leu114= Single submitter dystonic disorder
- p.Leu139= Single submitter dystonic disorder
- p.Leu161= Single submitter dystonic disorder
- p.Leu169= Single submitter dystonic disorder
- p.Leu180= Single submitter dystonic disorder
- p.Leu201= Single submitter dystonic disorder
- p.Leu222= Single submitter dystonic disorder
- p.Leu231= Single submitter dystonic disorder
- p.Leu241= Single submitter dystonic disorder
- p.Leu76= Single submitter dystonic disorder
- p.Leu80= Single submitter dystonic disorder
- p.Leu83= Single submitter dystonic disorder
- p.Leu86= Single submitter dystonic disorder
- p.Leu95= Single submitter dystonic disorder
- p.Lys174= Single submitter dystonic disorder
- p.Lys220= Single submitter dystonic disorder
- p.Lys90= Single submitter
- p.Phe181= Single submitter dystonic disorder
- p.Pro143= Single submitter dystonic disorder
- p.Pro87= Single submitter dystonic disorder
- p.Ser117= Single submitter dystonic disorder
- p.Ser156= Single submitter dystonic disorder
- p.Ser213= Single submitter dystonic disorder
- p.Ser243= Single submitter dystonic disorder
- p.Thr118= Single submitter dystonic disorder
- p.Thr151= Single submitter dystonic disorder
- p.Tyr259= Single submitter dystonic disorder
- p.Val112= Single submitter dystonic disorder
- p.Val138= Single submitter dystonic disorder
- p.Val183= Single submitter dystonic disorder
- p.Val193= Single submitter dystonic disorder
- p.Val214= Single submitter dystonic disorder
- p.Val256= Single submitter dystonic disorder
Uncertain significance 83
- c.304+5G>C Multiple submitters dystonic disorder
- p.Ala168Thr Multiple submitters Inborn genetic diseases ⚠
- p.Arg210Gln Multiple submitters dystonic disorder ⚠
- p.Arg219Gln Multiple submitters Inborn genetic diseases ⚠
- p.Arg65Trp Multiple submitters dystonic disorder ⚠
- p.Asn121Lys Multiple submitters dystonic disorder
- p.Asn122Ser Multiple submitters dystonic disorder ⚠
- p.Asn127Ser Multiple submitters dystonic disorder ⚠
- p.Gly110Arg Multiple submitters dopa-responsive dystonia due to sepiapterin reductase deficiency ⚠
- p.Met179Thr Multiple submitters dopa-responsive dystonia due to sepiapterin reductase deficiency ⚠
- p.Met218Ile Multiple submitters Inborn genetic diseases ⚠
- p.Pro89Leu Multiple submitters dopa-responsive dystonia due to sepiapterin reductase deficiency ⚠
- p.Ser103Cys Multiple submitters dystonic disorder ⚠
- p.Tyr259Cys Multiple submitters dystonic disorder
- p.Val112Leu Multiple submitters dystonic disorder ⚠
- p.Val256Met Multiple submitters dystonic disorder ⚠
- c.305-13del Single submitter
- c.596-4C>G Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- c.*108G>A Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- c.*233G>A Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- c.*321G>C Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- c.*377G>A Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- c.*400C>T Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- c.*410C>G Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- c.*50C>T Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- c.*575G>A Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- c.*597C>A Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- c.*607A>C Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Ala125Thr Single submitter dystonic disorder ⚠
- p.Ala175Thr Single submitter dystonic disorder ⚠
- p.Ala82Thr Single submitter dystonic disorder ⚠
- p.Arg177Gly Single submitter dystonic disorder ⚠
- p.Arg177His Single submitter dystonic disorder ⚠
- p.Arg88Gln Single submitter dystonic disorder ⚠
- p.Asn154Ile Single submitter Inborn genetic diseases ⚠
- p.Asp204His Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency ⚠
- p.Asp215Asn Single submitter dystonic disorder ⚠
- p.Asp215Tyr Single submitter dystonic disorder
- p.Asp257His Single submitter dystonic disorder ⚠
- p.Cys133Phe Single submitter dystonic disorder ⚠
- p.Cys159= Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Cys171Arg Single submitter ⚠
- p.Cys234Ser Single submitter dystonic disorder
- p.Gln119Pro Single submitter dystonic disorder ⚠
- p.Gly105Arg Single submitter ⚠
- p.Gly166Asp Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency ⚠
- p.Gly166Cys Single submitter dystonic disorder ⚠
- p.Gly199Arg Single submitter dystonic disorder ⚠
- p.Gly253Arg Single submitter dystonic disorder ⚠
- p.Leu104Phe Single submitter Inborn genetic diseases ⚠
- p.Leu104Pro Single submitter dystonic disorder ⚠
- p.Leu132Phe Single submitter dystonic disorder
- p.Leu158Phe Single submitter dystonic disorder ⚠
- p.Leu158Val Single submitter ⚠
- p.Leu161Arg Single submitter dystonic disorder ⚠
- p.Leu186Val Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency ⚠
- p.Leu23Met Single submitter dystonic disorder
- p.Leu244Ter Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Leu83Pro Single submitter dystonic disorder ⚠
- p.Leu86Phe Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency ⚠
- p.Leu95Val Single submitter dystonic disorder ⚠
- p.Lys165Gln Single submitter Inborn genetic diseases ⚠
- p.Lys261Arg Single submitter dystonic disorder ⚠
- p.Pro143Ala Single submitter dystonic disorder ⚠
- p.Pro143Arg Single submitter dystonic disorder ⚠
- p.Pro143Leu Single submitter Inborn genetic diseases ⚠
- p.Pro146Thr Single submitter dystonic disorder ⚠
- p.Pro189Leu Single submitter ⚠
- p.Pro200Ser Single submitter dystonic disorder ⚠
- p.Pro87Arg Single submitter dystonic disorder ⚠
- p.Pro87Thr Single submitter dystonic disorder ⚠
- p.Pro89Arg Single submitter dystonic disorder ⚠
- p.Ser103Pro Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency ⚠
- p.Ser136Cys Single submitter dystonic disorder ⚠
- p.Thr129Ile Single submitter Inborn genetic diseases ⚠
- p.Tyr123Cys Single submitter dystonic disorder ⚠
- p.Val152Ala Single submitter ⚠
- p.Val152Met Single submitter dystonic disorder ⚠
- p.Val236Leu Single submitter dystonic disorder ⚠
- p.Val36Met Single submitter dopa-responsive dystonia due to sepiapterin reductase deficiency ⚠
- p.Ile98del No assertion criteria dopa-responsive dystonia due to sepiapterin reductase deficiency
- p.Leu225Met No assertion criteria SPR-related disorder ⚠
- p.Trp124Arg No assertion criteria dopa-responsive dystonia due to sepiapterin reductase deficiency ⚠