USP8 — 184 ClinVar variants
All ClinVar germline USP8 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 84 flagged for review →
5 Pathogenic · 1 Conflicting · 25 Benign · 64 Likely benign · 89 Uncertain significance
Full USP8 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 84
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 lean, ClinVar uncertain 68
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
-
USP8 p.Phe875Ser
Uncertain significance
Multiple submitters
hereditary spastic paraplegia
-
USP8 p.Pro703His
Uncertain significance
Multiple submitters
hereditary spastic paraplegia
-
USP8 p.Ala533Thr
Uncertain significance
Single submitter
hereditary spastic paraplegia
- USP8 p.Ala684Asp Uncertain significance Single submitter
-
USP8 p.Ala798Gly
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Arg1112Gln
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Arg275Gln
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Arg275Trp
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Arg322Gln
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Arg620Lys
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Arg991Gln
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Asn172Ser
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Asn196Thr
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Asn764Ser
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Asn766Ser
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Asn815Asp
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Asp625Asn
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Gln165Leu
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Gln350His
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Gln487Arg
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Gln916Lys
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Glu341Gly
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Glu511Gln
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Glu558Asp
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Gly598Val
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Gly840Glu
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ile270Val
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ile330Val
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ile362Val
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ile377Val
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ile394Val
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ile514Val
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ile791Val
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Leu1109Ser
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Leu259Ile
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Leu268Val
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Leu90Phe
Uncertain significance
Single submitter
hereditary spastic paraplegia
- USP8 p.Leu954Pro Uncertain significance Single submitter
-
USP8 p.Leu995Val
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Lys171Asn
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Lys546Arg
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Lys96Gln
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Met525Leu
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Pro374Thr
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Pro383Gln
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Pro405Ser
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Pro576Ser
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Pro774Ala
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Pro774Ser
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ser1027Thr
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ser106Cys
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ser160Cys
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ser220Asn
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ser437Asn
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ser592Phe
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Thr1118Lys
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Thr177Ser
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Thr193Met
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Thr737Ile
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Tyr1040Cys
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Tyr749Cys
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Tyr85Ser
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Val289Ile
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Val296Ile
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Val381Ala
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Val384Asp
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Val648Ile
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ala225Thr
Uncertain significance
No assertion criteria
USP8-related disorder
Predictors split 16
The independent predictors disagree with each other — read with care.
-
USP8 p.Arg133Trp
Uncertain significance
Multiple submitters
hereditary spastic paraplegia
-
USP8 p.Arg763Trp
Benign
Multiple submitters
hereditary spastic paraplegia
-
USP8 p.Asn764Lys
Benign
Multiple submitters
hereditary spastic paraplegia
-
USP8 p.Ala948Pro
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Gln136Pro
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Gln310His
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Gln518Pro
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Glu642Ala
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Leu937Phe
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Lys1097Ile
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ser1098Ala
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
USP8 p.Ser641Asn
Uncertain significance
Single submitter
hereditary spastic paraplegia
- USP8 p.Gln310Lys Uncertain significance No assertion criteria
-
USP8 p.Pro720Arg
Pathogenic
No assertion criteria
Cushing disease due to pituitary adenoma
-
USP8 p.Ser718Cys
Pathogenic
No assertion criteria
Cushing disease due to pituitary adenoma
-
USP8 p.Ser718Pro
Pathogenic
No assertion criteria
Cushing disease due to pituitary adenoma
All USP8 variants
Pathogenic 5
- p.Arg991Ter Single submitter
- p.Pro720Arg No assertion criteria Cushing disease due to pituitary adenoma ⚠
- p.Ser718Cys No assertion criteria Cushing disease due to pituitary adenoma ⚠
- p.Ser718Pro No assertion criteria Cushing disease due to pituitary adenoma ⚠
- p.Ser719del No assertion criteria Cushing disease due to pituitary adenoma
Conflicting classifications of pathogenicity 1
- p.Arg444Cys Single submitter hereditary spastic paraplegia
Benign 25
- c.104+16C>T Multiple submitters hereditary spastic paraplegia
- c.250-8A>C Multiple submitters hereditary spastic paraplegia
- c.3038+16T>G Multiple submitters hereditary spastic paraplegia
- c.-58G>C Multiple submitters
- p.Ala348Thr Multiple submitters hereditary spastic paraplegia
- p.Arg483Gln Multiple submitters hereditary spastic paraplegia
- p.Arg763Trp Multiple submitters hereditary spastic paraplegia ⚠
- p.Asn764Lys Multiple submitters hereditary spastic paraplegia ⚠
- p.Asp443Gly Multiple submitters hereditary spastic paraplegia
- p.Gln432= Multiple submitters hereditary spastic paraplegia
- p.His559Tyr Multiple submitters hereditary spastic paraplegia
- p.Leu1011= Multiple submitters hereditary spastic paraplegia
- p.Leu134= Multiple submitters hereditary spastic paraplegia
- p.Leu268Ile Multiple submitters hereditary spastic paraplegia
- p.Leu837= Multiple submitters hereditary spastic paraplegia
- p.Lys388Glu Multiple submitters hereditary spastic paraplegia
- p.Lys506Gln Multiple submitters hereditary spastic paraplegia
- p.Phe619= Multiple submitters hereditary spastic paraplegia
- p.Thr739Ala Multiple submitters hereditary spastic paraplegia
- c.249+21_249+23del Single submitter hereditary spastic paraplegia
- c.2896-8dup Single submitter hereditary spastic paraplegia
- c.3172-16_3172-13dup Single submitter hereditary spastic paraplegia
- p.Glu488= Single submitter hereditary spastic paraplegia
- p.Lys195Glu Single submitter hereditary spastic paraplegia
- p.Thr351Met Single submitter hereditary spastic paraplegia
Likely benign 64
- p.Asn797= Multiple submitters hereditary spastic paraplegia
- p.Asp624= Multiple submitters hereditary spastic paraplegia
- p.Asp707= Multiple submitters hereditary spastic paraplegia
- p.Glu254= Multiple submitters hereditary spastic paraplegia
- p.Tyr1060= Multiple submitters hereditary spastic paraplegia
- c.104+17G>A Single submitter hereditary spastic paraplegia
- c.104+20A>G Single submitter hereditary spastic paraplegia
- c.1218+17A>T Single submitter hereditary spastic paraplegia
- c.1219-20C>G Single submitter hereditary spastic paraplegia
- c.1219-5T>C Single submitter
- c.1891-17T>A Single submitter hereditary spastic paraplegia
- c.1972-20T>G Single submitter hereditary spastic paraplegia
- c.2234+10T>A Single submitter hereditary spastic paraplegia
- c.2235-20G>T Single submitter hereditary spastic paraplegia
- c.2235-9C>T Single submitter hereditary spastic paraplegia
- c.250-15T>C Single submitter hereditary spastic paraplegia
- c.2658+21_2658+24dup Single submitter hereditary spastic paraplegia
- c.2658+5_2658+8dup Single submitter hereditary spastic paraplegia
- c.2658+9T>C Single submitter hereditary spastic paraplegia
- c.2895+3_2895+7dup Single submitter
- c.2896-9T>C Single submitter hereditary spastic paraplegia
- c.3038+22_3038+24del Single submitter hereditary spastic paraplegia
- c.3171+9C>A Single submitter hereditary spastic paraplegia
- c.499-13T>C Single submitter hereditary spastic paraplegia
- c.541+9G>A Single submitter hereditary spastic paraplegia
- c.542-19T>C Single submitter hereditary spastic paraplegia
- c.850-17G>T Single submitter hereditary spastic paraplegia
- p.Ala564= Single submitter hereditary spastic paraplegia
- p.Arg250= Single submitter
- p.Asn918= Single submitter
- p.Asp212Asn Single submitter hereditary spastic paraplegia
- p.Asp878= Single submitter
- p.Gln433= Single submitter hereditary spastic paraplegia
- p.Gln478= Single submitter hereditary spastic paraplegia
- p.Gln632= Single submitter hereditary spastic paraplegia
- p.Gln841= Single submitter hereditary spastic paraplegia
- p.Gln929= Single submitter hereditary spastic paraplegia
- p.Ile845= Single submitter hereditary spastic paraplegia
- p.Ile921= Single submitter hereditary spastic paraplegia
- p.Leu1035= Single submitter hereditary spastic paraplegia
- p.Leu158= Single submitter hereditary spastic paraplegia
- p.Leu188= Single submitter hereditary spastic paraplegia
- p.Leu339= Single submitter
- p.Leu364= Single submitter hereditary spastic paraplegia
- p.Leu455= Single submitter hereditary spastic paraplegia
- p.Leu614= Single submitter hereditary spastic paraplegia
- p.Leu795= Single submitter hereditary spastic paraplegia
- p.Lys517= Single submitter
- p.Phe769= Single submitter hereditary spastic paraplegia
- p.Pro1031= Single submitter hereditary spastic paraplegia
- p.Pro383Leu Single submitter hereditary spastic paraplegia
- p.Pro649= Single submitter hereditary spastic paraplegia
- p.Pro8= Single submitter
- p.Thr351= Single submitter hereditary spastic paraplegia
- p.Thr540= Single submitter hereditary spastic paraplegia
- p.Thr591= Single submitter hereditary spastic paraplegia
- p.Thr626= Single submitter hereditary spastic paraplegia
- p.Thr777= Single submitter hereditary spastic paraplegia
- p.Thr945= Single submitter
- p.Tyr12= Single submitter hereditary spastic paraplegia
- p.Tyr844= Single submitter hereditary spastic paraplegia
- p.Val1006= Single submitter hereditary spastic paraplegia
- p.Val257= Single submitter hereditary spastic paraplegia
- p.Val99= Single submitter hereditary spastic paraplegia
Uncertain significance 89
- p.Arg1112Ter Multiple submitters hereditary spastic paraplegia
- p.Arg133Trp Multiple submitters hereditary spastic paraplegia ⚠
- p.Phe875Ser Multiple submitters hereditary spastic paraplegia ⚠
- p.Pro703His Multiple submitters hereditary spastic paraplegia ⚠
- c.104+5G>C Single submitter hereditary spastic paraplegia
- c.2879_2895+12dup Single submitter hereditary spastic paraplegia
- c.335+4C>G Single submitter hereditary spastic paraplegia
- c.335+7A>G Single submitter hereditary spastic paraplegia
- p.Ala533Thr Single submitter hereditary spastic paraplegia ⚠
- p.Ala684Asp Single submitter ⚠
- p.Ala798Gly Single submitter hereditary spastic paraplegia ⚠
- p.Ala948Pro Single submitter hereditary spastic paraplegia ⚠
- p.Arg1112Gln Single submitter hereditary spastic paraplegia ⚠
- p.Arg275Gln Single submitter hereditary spastic paraplegia ⚠
- p.Arg275Trp Single submitter hereditary spastic paraplegia ⚠
- p.Arg322Gln Single submitter hereditary spastic paraplegia ⚠
- p.Arg322Ter Single submitter USP8-related disorder
- p.Arg620Lys Single submitter hereditary spastic paraplegia ⚠
- p.Arg991Gln Single submitter hereditary spastic paraplegia ⚠
- p.Asn172Ser Single submitter hereditary spastic paraplegia ⚠
- p.Asn196Thr Single submitter hereditary spastic paraplegia ⚠
- p.Asn764Ser Single submitter hereditary spastic paraplegia ⚠
- p.Asn766Ser Single submitter hereditary spastic paraplegia ⚠
- p.Asn815Asp Single submitter hereditary spastic paraplegia ⚠
- p.Asp625Asn Single submitter hereditary spastic paraplegia ⚠
- p.Gln136Pro Single submitter hereditary spastic paraplegia ⚠
- p.Gln165Leu Single submitter hereditary spastic paraplegia ⚠
- p.Gln310His Single submitter hereditary spastic paraplegia ⚠
- p.Gln350His Single submitter hereditary spastic paraplegia ⚠
- p.Gln487Arg Single submitter hereditary spastic paraplegia ⚠
- p.Gln518Pro Single submitter hereditary spastic paraplegia ⚠
- p.Gln916Lys Single submitter hereditary spastic paraplegia ⚠
- p.Glu341Gly Single submitter hereditary spastic paraplegia ⚠
- p.Glu511Gln Single submitter hereditary spastic paraplegia ⚠
- p.Glu558Asp Single submitter hereditary spastic paraplegia ⚠
- p.Glu642Ala Single submitter hereditary spastic paraplegia ⚠
- p.Gly598Val Single submitter hereditary spastic paraplegia ⚠
- p.Gly840Glu Single submitter hereditary spastic paraplegia ⚠
- p.Ile270Val Single submitter hereditary spastic paraplegia ⚠
- p.Ile330Val Single submitter hereditary spastic paraplegia ⚠
- p.Ile362Val Single submitter hereditary spastic paraplegia ⚠
- p.Ile377Val Single submitter hereditary spastic paraplegia ⚠
- p.Ile394Val Single submitter hereditary spastic paraplegia ⚠
- p.Ile514Val Single submitter hereditary spastic paraplegia ⚠
- p.Ile791Val Single submitter hereditary spastic paraplegia ⚠
- p.Leu1109Ser Single submitter hereditary spastic paraplegia ⚠
- p.Leu259Ile Single submitter hereditary spastic paraplegia ⚠
- p.Leu268Val Single submitter hereditary spastic paraplegia ⚠
- p.Leu90Phe Single submitter hereditary spastic paraplegia ⚠
- p.Leu937Phe Single submitter hereditary spastic paraplegia ⚠
- p.Leu954Pro Single submitter ⚠
- p.Leu995Val Single submitter hereditary spastic paraplegia ⚠
- p.Lys1097Ile Single submitter hereditary spastic paraplegia ⚠
- p.Lys171Asn Single submitter hereditary spastic paraplegia ⚠
- p.Lys248Ter Single submitter
- p.Lys546Arg Single submitter hereditary spastic paraplegia ⚠
- p.Lys96Gln Single submitter hereditary spastic paraplegia ⚠
- p.Met525Leu Single submitter hereditary spastic paraplegia ⚠
- p.Pro319fs Single submitter hereditary spastic paraplegia
- p.Pro374Thr Single submitter hereditary spastic paraplegia ⚠
- p.Pro383Gln Single submitter hereditary spastic paraplegia ⚠
- p.Pro405Ser Single submitter hereditary spastic paraplegia ⚠
- p.Pro435del Single submitter hereditary spastic paraplegia
- p.Pro576Ser Single submitter hereditary spastic paraplegia ⚠
- p.Pro774Ala Single submitter hereditary spastic paraplegia ⚠
- p.Pro774Ser Single submitter hereditary spastic paraplegia ⚠
- p.Ser1027Thr Single submitter hereditary spastic paraplegia ⚠
- p.Ser106Cys Single submitter hereditary spastic paraplegia ⚠
- p.Ser1098Ala Single submitter hereditary spastic paraplegia ⚠
- p.Ser160Cys Single submitter hereditary spastic paraplegia ⚠
- p.Ser220Asn Single submitter hereditary spastic paraplegia ⚠
- p.Ser437Asn Single submitter hereditary spastic paraplegia ⚠
- p.Ser592Phe Single submitter hereditary spastic paraplegia ⚠
- p.Ser641Asn Single submitter hereditary spastic paraplegia ⚠
- p.Ser817Ter Single submitter
- p.Thr1118Lys Single submitter hereditary spastic paraplegia ⚠
- p.Thr177Ser Single submitter hereditary spastic paraplegia ⚠
- p.Thr193Met Single submitter hereditary spastic paraplegia ⚠
- p.Thr737Ile Single submitter hereditary spastic paraplegia ⚠
- p.Tyr1040Cys Single submitter hereditary spastic paraplegia ⚠
- p.Tyr749Cys Single submitter hereditary spastic paraplegia ⚠
- p.Tyr85Ser Single submitter hereditary spastic paraplegia ⚠
- p.Val289Ile Single submitter hereditary spastic paraplegia ⚠
- p.Val296Ile Single submitter hereditary spastic paraplegia ⚠
- p.Val381Ala Single submitter hereditary spastic paraplegia ⚠
- p.Val384Asp Single submitter hereditary spastic paraplegia ⚠
- p.Val648Ile Single submitter hereditary spastic paraplegia ⚠
- p.Ala225Thr No assertion criteria USP8-related disorder ⚠
- p.Gln310Lys No assertion criteria ⚠