PRNP — 192 ClinVar variants
All ClinVar germline PRNP variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 76 flagged for review →
16 Pathogenic · 3 Pathogenic/Likely pathogenic · 8 Likely pathogenic · 7 Conflicting · 18 Benign · 12 Benign/Likely benign · 36 Likely benign · 92 Uncertain significance
Full PRNP gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 76
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 5
ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.
-
PRNP p.Ala117Val
Pathogenic
Multiple submitters
Inborn genetic diseases
-
PRNP p.Arg148His
Likely pathogenic
Multiple submitters
Huntington disease-like 1
-
PRNP p.Arg208His
Pathogenic/Likely pathogenic
Multiple submitters
Huntington disease-like 1
-
PRNP p.Ala133Val
Pathogenic
No assertion criteria
Gerstmann-Straussler-Scheinker syndrome
-
PRNP p.Glu211Gln
Pathogenic
No assertion criteria
inherited Creutzfeldt-Jakob disease
Predictors agree, ClinVar conflicts 3
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
-
PRNP p.Ala2Val
Conflicting
Single submitter
Inherited prion disease
-
PRNP p.Arg48His
Conflicting
Single submitter
Inherited prion disease
-
PRNP p.Pro39Leu
Conflicting
Single submitter
Inherited prion disease
Predictors lean, ClinVar uncertain 41
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
-
PRNP p.Met109Leu
Uncertain significance
Multiple submitters
Huntington disease-like 1
-
PRNP p.Met166Ile
Uncertain significance
Multiple submitters
kuru, susceptibility to
-
PRNP p.Met166Thr
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PRNP p.Met232Arg
Uncertain significance
Multiple submitters
kuru, susceptibility to
-
PRNP p.Pro239Ser
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PRNP p.Ser17Thr
Uncertain significance
Multiple submitters
Huntington disease-like 1
-
PRNP p.Ser97Asn
Uncertain significance
Multiple submitters
Huntington disease-like 1
-
PRNP p.Val189Ile
Uncertain significance
Multiple submitters
Inherited prion disease
-
PRNP p.Ala14Ser
Uncertain significance
Single submitter
Inborn genetic diseases
-
PRNP p.Arg151Cys
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Arg151His
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Arg208Cys
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Arg25His
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Asn171Lys
Uncertain significance
Single submitter
Huntington disease-like 1
- PRNP p.Asn174His Uncertain significance Single submitter
-
PRNP p.Asn47Asp
Uncertain significance
Single submitter
Huntington disease-like 1
- PRNP p.Asp144Glu Uncertain significance Single submitter
-
PRNP p.Cys179Gly
Uncertain significance
Single submitter
PRNP-related disorder
-
PRNP p.Glu168Gly
Uncertain significance
Single submitter
Inborn genetic diseases
- PRNP p.Glu219Gly Uncertain significance Single submitter
- PRNP p.Gly20Ser Uncertain significance Single submitter
-
PRNP p.Gly29Glu
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Gly56Ser
Uncertain significance
Single submitter
Inborn genetic diseases
-
PRNP p.Gly72Arg
Uncertain significance
Single submitter
Inborn genetic diseases
-
PRNP p.Gly82Arg
Uncertain significance
Single submitter
Inborn genetic diseases
- PRNP p.Ile138Met Uncertain significance Single submitter
- PRNP p.Ile139Val Uncertain significance Single submitter
-
PRNP p.Ile182Met
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Leu250Pro
Uncertain significance
Single submitter
Huntington disease-like 1
- PRNP p.Met232Ile Uncertain significance Single submitter
- PRNP p.Phe175Leu Uncertain significance Single submitter
- PRNP p.Pro158Leu Uncertain significance Single submitter
-
PRNP p.Pro26Ala
Uncertain significance
Single submitter
Inherited prion disease
- PRNP p.Pro26Leu Uncertain significance Single submitter
- PRNP p.Ser43Gly Uncertain significance Single submitter
-
PRNP p.Thr188Met
Uncertain significance
Single submitter
Huntington disease-like 1
- PRNP p.Thr95Asn Uncertain significance Single submitter
- PRNP p.Trp73Ser Uncertain significance Single submitter
-
PRNP p.Tyr169His
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Val252Ala
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Pro238Leu
Uncertain significance
No assertion criteria
vascular dementia
Predictors split 27
The independent predictors disagree with each other — read with care.
-
PRNP p.Arg151Leu
Uncertain significance
Multiple submitters
Huntington disease-like 1
-
PRNP p.Asp178Asn
Pathogenic/Likely pathogenic
Multiple submitters
PRNP-related disorder
-
PRNP p.Gln217Arg
Likely pathogenic
Multiple submitters
Huntington disease-like 1
-
PRNP p.Glu200Lys
Pathogenic
Multiple submitters
Huntington disease-like 1
-
PRNP p.Phe198Ser
Pathogenic
Multiple submitters
Huntington disease-like 1
-
PRNP p.Thr188Arg
Likely pathogenic
Multiple submitters
PRNP-related disorder
-
PRNP p.Arg136Ser
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Arg136Thr
Uncertain significance
Single submitter
Huntington disease-like 1
- PRNP p.Arg156His Uncertain significance Single submitter
-
PRNP p.Arg25Ser
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Arg37Gln
Uncertain significance
Single submitter
Inborn genetic diseases
-
PRNP p.Gln212Pro
Conflicting
Single submitter
Gerstmann-Straussler-Scheinker syndrome
-
PRNP p.Glu207Gly
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Glu211Asp
Uncertain significance
Single submitter
Huntington disease-like 1
- PRNP p.Glu221Lys Uncertain significance Single submitter
-
PRNP p.Gly114Val
Uncertain significance
Single submitter
PRNP-related disorder
- PRNP p.Gly30Arg Uncertain significance Single submitter
- PRNP p.Gly64Ser Uncertain significance Single submitter
- PRNP p.His77Tyr Uncertain significance Single submitter
-
PRNP p.Met134Ile
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Pro105Ser
Conflicting
Single submitter
PRNP-related disorder
-
PRNP p.Pro165Ser
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Thr107Ile
Uncertain significance
Single submitter
Huntington disease-like 1
- PRNP p.Thr193Ile Uncertain significance Single submitter
-
PRNP p.Tyr163His
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.Tyr225Cys
Uncertain significance
Single submitter
Huntington disease-like 1
-
PRNP p.His187Arg
Pathogenic
No assertion criteria
Gerstmann-Straussler-Scheinker syndrome
All PRNP variants
Pathogenic 16
- p.Ala117Val Multiple submitters Inborn genetic diseases ⚠
- p.Glu200Lys Multiple submitters Huntington disease-like 1 ⚠
- p.Phe198Ser Multiple submitters Huntington disease-like 1 ⚠
- p.Pro102Leu Multiple submitters spongiform encephalopathy with neuropsychiatric features
- p.Thr183Ala Multiple submitters Huntington disease-like 1
- p.Gln160Ter Single submitter Huntington disease-like 1
- p.Gln91_Gly92insProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGln Single submitter PRNP-associated condition
- p.Pro105Leu Single submitter Inborn genetic diseases
- c.154_177[6_13] No assertion criteria Inherited prion disease
- p.Ala133Val No assertion criteria Gerstmann-Straussler-Scheinker syndrome ⚠
- p.Gln227Ter No assertion criteria Gerstmann-Straussler-Scheinker syndrome
- p.Glu211Gln No assertion criteria inherited Creutzfeldt-Jakob disease ⚠
- p.His187Arg No assertion criteria Gerstmann-Straussler-Scheinker syndrome ⚠
- p.Pro105Thr No assertion criteria spongiform encephalopathy with neuropsychiatric features
- p.Tyr145Ter No assertion criteria CEREBRAL AMYLOID ANGIOPATHY, PRNP-RELATED
- p.Tyr163Ter No assertion criteria CEREBRAL AMYLOID ANGIOPATHY, PRNP-RELATED
Pathogenic/Likely pathogenic 3
- p.Arg208His Multiple submitters Huntington disease-like 1 ⚠
- p.Asp178Asn Multiple submitters PRNP-related disorder ⚠
- p.Gly131Val Multiple submitters Gerstmann-Straussler-Scheinker syndrome
Likely pathogenic 8
- p.Arg148His Multiple submitters Huntington disease-like 1 ⚠
- p.Gln217Arg Multiple submitters Huntington disease-like 1 ⚠
- p.Thr188Arg Multiple submitters PRNP-related disorder ⚠
- p.Ala118Val Single submitter Gerstmann-Straussler-Scheinker syndrome
- p.Gln91_Gly92insProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGln Single submitter Huntington disease-like 1
- p.Gly131Glu Single submitter Gerstmann-Straussler-Scheinker syndrome
- p.Tyr226Ter Single submitter
- p.Pro102Ser No assertion criteria Gerstmann-Straussler-Scheinker syndrome
Conflicting classifications of pathogenicity 7
- p.Ala2Val Single submitter Inherited prion disease ⚠
- p.Arg48His Single submitter Inherited prion disease ⚠
- p.Asp202= Single submitter Huntington disease-like 1
- p.Gln212Pro Single submitter Gerstmann-Straussler-Scheinker syndrome ⚠
- p.Gln91_Gly92insProHisGlyGlyGlyTrpGlyGln Single submitter PRNP-related disorder
- p.Pro105Ser Single submitter PRNP-related disorder ⚠
- p.Pro39Leu Single submitter Inherited prion disease ⚠
Benign 18
- c.-10-21G>A Multiple submitters
- c.*206A>G Multiple submitters Inherited prion disease
- c.*4A>T Multiple submitters Inherited prion disease
- c.*682A>G Multiple submitters Inherited prion disease
- c.*697A>G Multiple submitters Inherited prion disease
- p.Asn171Ser Multiple submitters Inherited prion disease
- p.Glu219Lys Multiple submitters Inherited prion disease
- p.Gly82= Multiple submitters Huntington disease-like 1
- p.Pro84= Multiple submitters Inherited prion disease
- c.-18C>T Single submitter Inherited prion disease
- c.*1063G>A Single submitter Inherited prion disease
- c.*1412T>A Single submitter Inherited prion disease
- c.*482A>G Single submitter Inherited prion disease
- c.*592T>C Single submitter Inherited prion disease
- c.*672C>G Single submitter Inherited prion disease
- c.*800C>T Single submitter Inherited prion disease
- c.*936C>T Single submitter Inherited prion disease
- p.Gly40= Single submitter Huntington disease-like 1
Benign/Likely benign 12
- c.*70G>A Multiple submitters Inherited prion disease
- p.60_67PHGGGWGQ[3] Multiple submitters Huntington disease-like 1
- p.Ala117= Multiple submitters Inherited prion disease
- p.Gly124= Multiple submitters Huntington disease-like 1
- p.Gly142Ser Multiple submitters Inherited prion disease
- p.Gly53= Multiple submitters Gerstmann-Straussler-Scheinker syndrome
- p.Gly54Ser Multiple submitters Inherited prion disease
- p.Met129Val Multiple submitters fatal familial insomnia
- p.Pro102= Multiple submitters Huntington disease-like 1
- p.Pro68= Multiple submitters Huntington disease-like 1
- p.Pro76= Multiple submitters Inherited prion disease
- p.Pro84_Gln91del Multiple submitters spongiform encephalopathy with neuropsychiatric features
Likely benign 36
- p.Gln212= Multiple submitters kuru, susceptibility to
- p.Gln75= Multiple submitters Huntington disease-like 1
- p.His177= Multiple submitters Inborn genetic diseases
- p.Thr188= Multiple submitters Huntington disease-like 1
- p.Tyr218= Multiple submitters Inherited prion disease
- c.-4C>T Single submitter
- p.Ala2= Single submitter Huntington disease-like 1
- p.Arg136= Single submitter Huntington disease-like 1
- p.Arg208= Single submitter Huntington disease-like 1
- p.Arg228= Single submitter Huntington disease-like 1
- p.Asn173= Single submitter Huntington disease-like 1
- p.Asn197= Single submitter Huntington disease-like 1
- p.Asp147= Single submitter Huntington disease-like 1
- p.Asp18= Single submitter Huntington disease-like 1
- p.Cys179= Single submitter Huntington disease-like 1
- p.Gln160= Single submitter Huntington disease-like 1
- p.Gly131= Single submitter Huntington disease-like 1
- p.Gly46= Single submitter Huntington disease-like 1
- p.Gly54= Single submitter Huntington disease-like 1
- p.His111= Single submitter Huntington disease-like 1
- p.Leu11= Single submitter Huntington disease-like 1
- p.Leu19= Single submitter Huntington disease-like 1
- p.Leu234Phe Single submitter Huntington disease-like 1
- p.Lys24= Single submitter Huntington disease-like 1
- p.Phe141= Single submitter Huntington disease-like 1
- p.Pro26= Single submitter
- p.Pro39= Single submitter Huntington disease-like 1
- p.Ser222= Single submitter Huntington disease-like 1
- p.Thr192= Single submitter Huntington disease-like 1
- p.Thr199= Single submitter
- p.Thr201= Single submitter Huntington disease-like 1
- p.Tyr169= Single submitter Huntington disease-like 1
- p.Tyr225= Single submitter
- p.Val122= Single submitter Huntington disease-like 1
- p.Val161= Single submitter
- c.*5G>A No assertion criteria PRNP-related disorder
Uncertain significance 92
- c.*115G>A Multiple submitters Gerstmann-Straussler-Scheinker syndrome
- p.60PHGGGWGQ[3] Multiple submitters Huntington disease-like 1
- p.Arg151Leu Multiple submitters Huntington disease-like 1 ⚠
- p.Met109Leu Multiple submitters Huntington disease-like 1 ⚠
- p.Met166Ile Multiple submitters kuru, susceptibility to ⚠
- p.Met166Thr Multiple submitters Inborn genetic diseases ⚠
- p.Met232Arg Multiple submitters kuru, susceptibility to ⚠
- p.Pro239Ser Multiple submitters Inborn genetic diseases ⚠
- p.Ser17Thr Multiple submitters Huntington disease-like 1 ⚠
- p.Ser97Asn Multiple submitters Huntington disease-like 1 ⚠
- p.Val189Ile Multiple submitters Inherited prion disease ⚠
- c.-21G>T Single submitter Inherited prion disease
- c.*1035T>G Single submitter Inherited prion disease
- c.*1134T>A Single submitter Inherited prion disease
- c.*1193G>A Single submitter Inherited prion disease
- c.*1281A>G Single submitter Inherited prion disease
- c.*1328T>C Single submitter Inherited prion disease
- c.*1466G>C Single submitter Inherited prion disease
- c.*1588C>T Single submitter Inherited prion disease
- c.*216G>A Single submitter Inherited prion disease
- c.*358C>A Single submitter Inherited prion disease
- c.*407T>G Single submitter Inherited prion disease
- c.*460G>T Single submitter Inherited prion disease
- c.*874C>T Single submitter Inherited prion disease
- c.*994C>T Single submitter Inherited prion disease
- p.60_67PHGGGWGQ[2] Single submitter Huntington disease-like 1
- p.Ala14Ser Single submitter Inborn genetic diseases ⚠
- p.Arg136Ser Single submitter Huntington disease-like 1 ⚠
- p.Arg136Thr Single submitter Huntington disease-like 1 ⚠
- p.Arg151Cys Single submitter Huntington disease-like 1 ⚠
- p.Arg151His Single submitter Huntington disease-like 1 ⚠
- p.Arg156His Single submitter ⚠
- p.Arg208Cys Single submitter Huntington disease-like 1 ⚠
- p.Arg25His Single submitter Huntington disease-like 1 ⚠
- p.Arg25Ser Single submitter Huntington disease-like 1 ⚠
- p.Arg37Gln Single submitter Inborn genetic diseases ⚠
- p.Asn171Lys Single submitter Huntington disease-like 1 ⚠
- p.Asn174His Single submitter ⚠
- p.Asn47Asp Single submitter Huntington disease-like 1 ⚠
- p.Asp144Glu Single submitter ⚠
- p.Cys179Gly Single submitter PRNP-related disorder ⚠
- p.Gln91_Gly92insProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGln Single submitter Huntington disease-like 1
- p.Glu168Gly Single submitter Inborn genetic diseases ⚠
- p.Glu207Gly Single submitter Huntington disease-like 1 ⚠
- p.Glu211Asp Single submitter Huntington disease-like 1 ⚠
- p.Glu219Gly Single submitter ⚠
- p.Glu221Lys Single submitter ⚠
- p.Gly114Val Single submitter PRNP-related disorder ⚠
- p.Gly20Ser Single submitter ⚠
- p.Gly29Glu Single submitter Huntington disease-like 1 ⚠
- p.Gly30Arg Single submitter ⚠
- p.Gly56Ser Single submitter Inborn genetic diseases ⚠
- p.Gly64Ser Single submitter ⚠
- p.Gly66= Single submitter spongiform encephalopathy with neuropsychiatric features
- p.Gly70Val Single submitter Inborn genetic diseases
- p.Gly72Arg Single submitter Inborn genetic diseases ⚠
- p.Gly82Arg Single submitter Inborn genetic diseases ⚠
- p.Gly92Glu Single submitter
- p.Gly93Asp Single submitter Huntington disease-like 1
- p.His69Leu Single submitter Gerstmann-Straussler-Scheinker syndrome
- p.His77Tyr Single submitter ⚠
- p.His96Asp Single submitter Inborn genetic diseases
- p.Ile138Met Single submitter ⚠
- p.Ile139Val Single submitter ⚠
- p.Ile182Met Single submitter Huntington disease-like 1 ⚠
- p.Leu250Pro Single submitter Huntington disease-like 1 ⚠
- p.Met134Ile Single submitter Huntington disease-like 1 ⚠
- p.Met154Ile Single submitter Huntington disease-like 1
- p.Met232Ile Single submitter ⚠
- p.Phe175Leu Single submitter ⚠
- p.Pro158Leu Single submitter ⚠
- p.Pro165Ser Single submitter Huntington disease-like 1 ⚠
- p.Pro239del Single submitter
- p.Pro26Ala Single submitter Inherited prion disease ⚠
- p.Pro26Leu Single submitter ⚠
- p.Pro60= Single submitter spongiform encephalopathy with neuropsychiatric features
- p.Ser237del Single submitter
- p.Ser43Gly Single submitter ⚠
- p.Thr107Ile Single submitter Huntington disease-like 1 ⚠
- p.Thr188Met Single submitter Huntington disease-like 1 ⚠
- p.Thr193Ile Single submitter ⚠
- p.Thr95Asn Single submitter ⚠
- p.Trp73Ser Single submitter ⚠
- p.Tyr149Ter Single submitter Huntington disease-like 1
- p.Tyr163His Single submitter Huntington disease-like 1 ⚠
- p.Tyr169His Single submitter Huntington disease-like 1 ⚠
- p.Tyr218Ter Single submitter Huntington disease-like 1
- p.Tyr225Cys Single submitter Huntington disease-like 1 ⚠
- p.Val209Met Single submitter Huntington disease-like 1
- p.Val252Ala Single submitter Huntington disease-like 1 ⚠
- p.Val252Met Single submitter Inborn genetic diseases
- p.Pro238Leu No assertion criteria vascular dementia ⚠