VCP (P55072) variants and mutations
VCP (also known as P55072) is a human protein-coding gene encoding a transitional endoplasmic reticulum ATPase protein. It uses ATP to extract ubiquitinated proteins from complexes or membranes for recycling or degradation and is central to proteostasis, ER-associated degradation, and autophagy. Dominant pathogenic variants cause multisystem proteinopathy with inclusion-body myopathy, Paget disease, frontotemporal dementia, or ALS. This analysis covers 792 VCP variants and mutations. Of these, 70% have computational variant effect predictions. Disease context includes inclusion body myopathy with Paget disease of bone and frontotemporal dementia t, frontotemporal dementia and/or amyotrophic lateral sclerosis 6, and inclusion body myopathy with Paget disease of bone and frontotemporal dementia. Example VCP variants include A2S, G4E, and G4R.
Variant analysis overview
- Gene: VCP
- Protein: P55072
- UniProt accession: P55072
- Organism: Homo sapiens
- Variants analyzed: 792
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 529 unspecified-consequence records; 6 stop lost; 1 stop retained variant; 13 frameshift variants; 111 synonymous variants; 114 missense variants; 7 stop-gained variants; 2 splice-region variants; 1 in-frame deletions; 8 substitution
- Prediction scores: 558 variants have prediction scores (70% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: inclusion body myopathy with Paget disease of bone and frontotemporal dementia t, frontotemporal dementia and/or amyotrophic lateral sclerosis 6, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, Charcot-Marie-Tooth disease type 2Y, amyotrophic lateral sclerosis, hereditary disease, neurodegenerative disease, frontotemporal dementia with motor neuron disease, cystic fibrosis, holoprosencephaly, Intellectual disability, neurodevelopmental disorder.
Protein structure and variant hotspots
- Protein features: 4 binding sites; 18 post-translational modification sites.
- PTM context: 12 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable VCP variants
Examples include A2S, G4E, G4R, G4V, A5V, G9D, G9V, D10E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2S (p.Ala2Ser), gnomAD rs1191632244, REVEL 0.23, CADD 22.60, Uncertain significance, Inborn genetic diseases
- G4E (p.Gly4Glu), rs767081097, ClinGen CA373297821, ClinVar RCV003139273, ClinVar RCV003778817, REVEL 0.23, CADD 23.10, Uncertain significance, not provided; Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; In
- G4R (p.Gly4Arg), rs2131047437, ClinGen CA373297835, ClinVar RCV001754958, Ensembl rs2131047437, REVEL 0.36, CADD 25.10, Uncertain significance, not provided
- G4V (p.Gly4Val), ExAC rs767081097, TOPMed rs767081097, gnomAD rs767081097, REVEL 0.33, CADD 24.70, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- A5V (p.Ala5Val), Ensembl rs1587135687, REVEL 0.31, CADD 23.60
- G9D (p.Gly9Asp), ExAC rs751227891, gnomAD rs751227891, REVEL 0.31, CADD 21.10
- G9V (p.Gly9Val), NCI-TCGA Cosmic COSV6272, REVEL 0.27, CADD 22.10, Variant assessed as somatic; moderate impact.
- D10E (p.Asp10Glu), rs1828874096, ClinGen CA373295390, ClinVar RCV001198195, Ensembl rs1828874096, AlphaMissense 0.09, MetaLR 0.62, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia t
- D10G (p.Asp10Gly), Ensembl rs1051383927, REVEL 0.57, CADD 23.60
- D11A (p.Asp11Ala), NCI-TCGA TCGA novel, Ensembl rs1587130735, Variant assessed as somatic; high impact.
- D11N (p.Asp11Asn), rs932872788, NCI-TCGA Cosmic COSV6272, Ensembl rs932872788, AlphaMissense 0.30, MetaLR 0.83, Variant assessed as somatic; moderate impact.
- T14I (p.Thr14Ile), rs1219381953, ClinGen CA373295294, ClinVar RCV001095442, ClinVar RCV001196071, REVEL 0.67, AlphaMissense 0.65, Uncertain significance, not specified; Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; I
- Q19R (p.Gln19Arg), rs553273871, ClinGen CA5039560, ClinVar RCV003139270, 1000Genomes rs553273871, REVEL 0.33, AlphaMissense 0.07, Uncertain significance, not provided
- K20N (p.Lys20Asn), rs1398452987, ClinGen CA373295188, ClinVar RCV002865098, gnomAD rs1398452987, REVEL 0.68, AlphaMissense 0.27, Uncertain significance, Inborn genetic diseases
- N21S (p.Asn21Ser), rs1409460709, ClinGen CA373295168, ClinVar RCV001900926, ClinVar RCV005298921, REVEL 0.29, AlphaMissense 0.15, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- R22C (p.Arg22Cys), gnomAD rs1158843378
- R22H (p.Arg22His), NCI-TCGA Cosmic COSV6272, REVEL 0.47, CADD 23.20, Variant assessed as somatic; moderate impact.
- P23L (p.Pro23Leu), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- N24T (p.Asn24Thr), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- R25Q (p.Arg25Gln), TOPMed rs1190481931, REVEL 0.76, CADD 25.50, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- R25W (p.Arg25Trp), rs920962883, ClinGen CA192683344, ClinVar RCV001962627, ClinVar RCV003136340, REVEL 0.91, CADD 28.10, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- I27V (p.Ile27Val), rs140913250, ClinGen CA5039558, ClinVar RCV000390549, ClinVar RCV000639655, REVEL 0.25, CADD 19.50, Benign/Likely benign, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- V28I (p.Val28Ile), rs1480586527, ClinGen CA373295071, ClinVar RCV001933553, TOPMed rs1480586527, AlphaMissense 0.31, MetaLR 0.81, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- V28L (p.Val28Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E30K (p.Glu30Lys), NCI-TCGA Cosmic COSV6272, Variant assessed as somatic; moderate impact.
- A31S (p.Ala31Ser), rs1828872997, ClinGen CA373294992, ClinVar RCV001768751, ClinVar RCV002449411, AlphaMissense 0.10, MetaLR 0.50, Uncertain significance, Inborn genetic diseases; not provided
- A31T (p.Ala31Thr), TOPMed rs1828872997, Uncertain significance
- I32V (p.Ile32Val), rs1828872947, ClinGen CA373294974, ClinVar RCV001319074, Ensembl rs1828872947, REVEL 0.28, CADD 18.80, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- N33S (p.Asn33Ser), gnomAD rs1351617227, REVEL 0.35, CADD 22.50, Uncertain significance, not provided
- S37G (p.Ser37Gly), TOPMed rs1828872706
- S42P (p.Ser42Pro), rs1238589369, ClinGen CA373294703, ClinVar RCV003443515, TOPMed rs1238589369, REVEL 0.81, CADD 25.60, Uncertain significance, not provided
- P44S (p.Pro44Ser), gnomAD 9-35057192-G-A, CADD 10.20
- P44A (p.Pro44Ala), gnomAD 9-35057192-G-C, CADD 10.90
- D47N (p.Asp47Asn), TOPMed rs1828867918
- E48Q (p.Glu48Gln), Ensembl rs1828867843
- E48K (p.Glu48Lys), gnomAD 9-35057210-C-T, CADD 9.66
- L49S (p.Leu49Ser), rs2490373969, ClinGen CA373294519, ClinVar RCV003231999, NCI-TCGA TCGA novel, Uncertain significance, not provided
- Q50R (p.Gln50Arg), TOPMed rs1458088202, gnomAD rs1458088202, REVEL 0.57, CADD 23.30
- p.Gln76 Ter77delinsArg, rs759030803, gnomAD 9-35057137-CATT-C, CADD 18.80
- R53* (p.Arg53Ter), ExAC rs774641311, gnomAD rs774641311, CADD 36.00
- R53Q (p.Arg53Gln), gnomAD rs1170154132, REVEL 0.78, CADD 24.90
- G54R (p.Gly54Arg), gnomAD 9-35057204-C-T, CADD 7.14
- D55V (p.Asp55Val), gnomAD rs1224146431, REVEL 0.96, CADD 28.80
- T56A (p.Thr56Ala), rs2490373952, ClinGen CA373294389, ClinVar RCV003425656, Likely pathogenic, not provided
- K62N (p.Lys62Asn), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- K62R (p.Lys62Arg), rs886063892, ClinGen CA10633918, ClinVar RCV000351753, ClinVar RCV000396114, REVEL 0.48, CADD 22.90, Uncertain significance, not provided; Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; In
- K63N (p.Lys63Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R65Q (p.Arg65Gln), rs2490373887, ClinGen CA373294172, ClinVar RCV003028220, ClinVar RCV003138441, REVEL 0.56, AlphaMissense 0.42, Uncertain significance, not provided; Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; In
- E66D (p.Glu66Asp), ExAC rs773319803, gnomAD rs773319803, REVEL 0.39, CADD 17.30
- A67V (p.Ala67Val), rs1487979155, TOPMed rs1487979155, gnomAD rs1487979155, REVEL 0.37, CADD 23.40, Variant assessed as somatic; moderate impact.
- C69R (p.Cys69Arg), rs1442790356, gnomAD 9-35057156-A-G, CADD 8.52
- I70V (p.Ile70Val), TOPMed rs1828866436
- I70L (p.Ile70Leu), rs1563975034, gnomAD 9-35057153-T-G, CADD 6.21
- V71I (p.Val71Ile), rs748091463, ClinGen CA5039531, NCI-TCGA Cosmic COSV6272, ClinVar RCV003066759, REVEL 0.37, CADD 22.30, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- S73* (p.Ser73Ter), rs1828626164, gnomAD 9-35057185-G-C, REVEL 0.40, CADD 19.00
- T76A (p.Thr76Ala), TOPMed rs1828866140
- C77F (p.Cys77Phe), rs754802166, ClinGen CA373293910, ClinVar RCV003231998, REVEL 0.77, CADD 24.50, Uncertain significance, not provided
- C77G (p.Cys77Gly), ExAC rs781182130, gnomAD rs781182130, REVEL 0.80, CADD 24.70
- C77Y (p.Cys77Tyr), rs754802166, ClinGen CA5039529, ClinVar RCV003786885, ExAC rs754802166, REVEL 0.78, CADD 24.30, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- S78C (p.Ser78Cys), rs1252437282, ClinGen CA373293873, ClinVar RCV001927107, TOPMed rs1252437282, REVEL 0.62, CADD 27.90, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- D79E (p.Asp79Glu), rs746810092, ClinGen CA5039528, ClinVar RCV001313680, ClinVar RCV003222301, REVEL 0.34, CADD 16.40, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- D79V (p.Asp79Val), NCI-TCGA Cosmic COSV6272, Variant assessed as somatic; moderate impact.
- I82L (p.Ile82Leu), rs1828865716, ClinGen CA373293765, ClinVar RCV003798451, TOPMed rs1828865716, AlphaMissense 0.28, MetaLR 0.68, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- R83Q (p.Arg83Gln), NCI-TCGA Cosmic COSV6271, gnomAD rs1828865639, REVEL 0.69, CADD 23.60, Variant assessed as somatic; moderate impact.
- R83W (p.Arg83Trp), NCI-TCGA Cosmic COSV6272, REVEL 0.92, CADD 32.00, Variant assessed as somatic; moderate impact.
- M84I (p.Met84Ile), NCI-TCGA TCGA novel, REVEL 0.53, CADD 22.00, Variant assessed as somatic; moderate impact.
- R86* (p.Arg86Ter), Ensembl rs866052069
- R86K (p.Arg86Lys), gnomAD rs1828865507, REVEL 0.40, CADD 19.60
- V88I (p.Val88Ile), Ensembl rs1828865391, REVEL 0.35, AlphaMissense 0.16, Uncertain significance, not provided
- R89Q (p.Arg89Gln), rs900105227, ClinGen CA192683160, ClinVar RCV002927327, Ensembl rs900105227, AlphaMissense 0.95, MetaLR 0.96, Pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- R89W (p.Arg89Trp), rs1828865320, ClinGen CA373293559, ClinVar RCV001308126, ClinVar RCV004720847, AlphaMissense 0.99, MetaLR 0.96, Conflicting interpretations, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- N90D (p.Asn90Asp), rs1828865209, ClinGen CA373293547, ClinVar RCV001325031, Ensembl rs1828865209, AlphaMissense 0.52, MetaLR 0.54, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- N91K (p.Asn91Lys), rs1563980966, ClinGen CA373293471, ClinVar RCV002015462, Ensembl rs1563980966, AlphaMissense 1.00, MetaLR 0.84, Likely pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- N91Y (p.Asn91Tyr), rs863225291, ClinGen CA279635, ClinVar RCV000201935, ClinVar RCV001271081, AlphaMissense 0.97, MetaLR 0.86, Pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- L92F (p.Leu92Phe), Ensembl rs1828865027
- R93C (p.Arg93Cys), rs1554669087, ClinGen CA373293400, ClinVar RCV000728008, ClinVar RCV002233733, REVEL 0.74, AlphaMissense 0.97, Pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- R93H (p.Arg93His), rs779959657, ClinGen CA5039527, ClinVar RCV000520021, ClinVar RCV002231635, REVEL 0.88, CADD 26.30, Conflicting interpretations, not provided; Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; In
- V94A (p.Val94Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V94L (p.Val94Leu), Ensembl rs1038579230
- R95C (p.Arg95Cys), rs121909332, ClinGen CA10603200, ClinVar RCV000280148, ClinVar RCV000761344, REVEL 0.61, AlphaMissense 0.69, Conflicting interpretations, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- R95G (p.Arg95Gly), rs121909332, ClinGen CA254402, ClinVar RCV000008992, ClinVar RCV005222674, AlphaMissense 0.69, MetaLR 0.66, Pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- R95H (p.Arg95His), rs758169026, ClinGen CA5039526, ClinVar RCV002018336, ExAC rs758169026, REVEL 0.46, AlphaMissense 0.30, Likely pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- R95P (p.Arg95Pro), rs758169026, ClinGen CA373293355, ClinVar RCV000731593, ClinVar RCV001046936, AlphaMissense 0.30, MetaLR 0.52, Conflicting interpretations, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- R95S (p.Arg95Ser), rs121909332, ClinGen CA373293362, ClinVar RCV003813702, AlphaMissense 0.69, MetaLR 0.66, Likely pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- G97E (p.Gly97Glu), rs864309502, ClinGen CA213389, ClinVar RCV000202492, ClinVar RCV001853259, AlphaMissense 0.97, MetaLR 0.89, Pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- D98E (p.Asp98Glu), rs1828864269, ClinGen CA373293267, ClinVar RCV001253196, Ensembl rs1828864269, AlphaMissense 0.89, MetaLR 0.78, Likely pathogenic, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia t
- I100L (p.Ile100Leu), ExAC rs753221407, gnomAD rs753221407, REVEL 0.62, CADD 24.20, Uncertain significance
- I100M (p.Ile100Met), TOPMed rs1828864042
- I100V (p.Ile100Val), rs753221407, ClinGen CA5039522, ClinVar RCV002296567, ExAC rs753221407, REVEL 0.13, CADD 18.60, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- I102T (p.Ile102Thr), gnomAD rs1412496313, REVEL 0.82, CADD 24.30
- Q103H (p.Gln103His), ExAC rs755519508, REVEL 0.41, CADD 17.30
- P104S (p.Pro104Ser), rs1186937475, ClinGen CA373292746, ClinVar RCV001863821, TOPMed rs1186937475, REVEL 0.45, CADD 22.80, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- C105R (p.Cys105Arg), rs1828842736, ClinGen CA373292734, ClinVar RCV001234395, Ensembl rs1828842736, AlphaMissense 0.96, MetaLR 0.68, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- D107V (p.Asp107Val), rs1563980440, ClinGen CA373292638, ClinVar RCV002233639, Ensembl rs1563980440, AlphaMissense 0.81, MetaLR 0.94, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- Y110D (p.Tyr110Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G111S (p.Gly111Ser), rs752038734, ClinGen CA5039499, ClinVar RCV001347828, ExAC rs752038734, REVEL 0.84, CADD 26.40, Pathogenic/Likely pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- K112R (p.Lys112Arg), rs766787045, ClinGen CA5039498, ClinVar RCV001168240, ClinVar RCV001168241, REVEL 0.61, CADD 22.90, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- R113H (p.Arg113His), rs2490370479, ClinGen CA373292435, ClinVar RCV002283218, ClinVar RCV006558749, Uncertain significance, not provided; Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; In
- I114V (p.Ile114Val), rs549915384, ClinGen CA5039496, ClinVar RCV000733637, ClinVar RCV000801185, REVEL 0.39, CADD 17.90, Conflicting interpretations, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- H115Y (p.His115Tyr), rs777887584, gnomAD 9-35057150-G-A, CADD 6.67
- I119V (p.Ile119Val), rs776815786, ClinGen CA5039493, ClinVar RCV002582023, ExAC rs776815786, REVEL 0.34, CADD 21.70, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- D120G (p.Asp120Gly), TOPMed rs1828841486
- T122I (p.Thr122Ile), rs2131038987, ClinGen CA373292175, ClinVar RCV001904683, Ensembl rs2131038987, AlphaMissense 0.99, MetaLR 0.96, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- V123L (p.Val123Leu), rs2131038977, ClinGen CA373292169, ClinVar RCV003804131, AlphaMissense 0.65, MetaLR 0.92, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- V123M (p.Val123Met), rs2131038977, ClinGen CA373292171, ClinVar RCV001891465, Ensembl rs2131038977, AlphaMissense 0.65, MetaLR 0.92, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- G125A (p.Gly125Ala), Ensembl rs1563980403, Likely pathogenic
- G125D (p.Gly125Asp), rs1563980403, ClinGen CA373292088, ClinVar RCV001809749, ClinVar RCV002233201, AlphaMissense 0.84, MetaLR 0.95, Conflicting interpretations, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- I126F (p.Ile126Phe), UniProt VAR 076465, Uncertain significance, in IBMPFD1
- I126S (p.Ile126Ser), rs1828841085, ClinGen CA373292055, ClinVar RCV001212180, Ensembl rs1828841085, AlphaMissense 0.99, MetaLR 0.91, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- T127A (p.Thr127Ala), gnomAD rs1287162663, REVEL 0.65, AlphaMissense 0.17
- T127I (p.Thr127Ile), rs2490370348, ClinGen CA373292001, ClinVar RCV002304637, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- G128A (p.Gly128Ala), rs1554668979, ClinGen CA373291969, ClinVar RCV000498690, ClinVar RCV003766796, AlphaMissense 0.93, MetaLR 0.95, Conflicting interpretations, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- G128R (p.Gly128Arg), rs2490370338, ClinGen CA373291997, ClinVar RCV003782738, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- G128S (p.Gly128Ser), rs2490370338, ClinGen CA373291998, ClinVar RCV002876342, Likely pathogenic, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- F131S (p.Phe131Ser), rs2490370305, ClinGen CA373291907, ClinVar RCV003139269, Uncertain significance, not provided
- V133I (p.Val133Ile), ExAC rs775567003, gnomAD rs775567003, Uncertain significance, not provided
- V133L (p.Val133Leu), rs775567003, ClinGen CA5039490, ClinVar RCV003089263, ClinVar RCV004763532, REVEL 0.56, CADD 21.90, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- Y134C (p.Tyr134Cys), rs1828840466, ClinGen CA373291813, ClinVar RCV001296826, ClinVar RCV002357086, AlphaMissense 0.87, MetaLR 0.94, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- Y134F (p.Tyr134Phe), rs1828840466, ClinGen CA373291811, ClinVar RCV003798813, AlphaMissense 0.87, MetaLR 0.94, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- Y134H (p.Tyr134His), rs2490370273, ClinGen CA373291815, ClinVar RCV003064048, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- Y134N (p.Tyr134Asn), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- K136T (p.Lys136Thr), rs2490370263, ClinGen CA373291761, ClinVar RCV002299369, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- P137L (p.Pro137Leu), Ensembl rs868435969, REVEL 0.88, CADD 29.40, Pathogenic/Likely pathogenic, Charcot-Marie-Tooth disease type 2Y; Inclusion body myopathy with Paget disease
- P137S (p.Pro137Ser), rs866101707, ClinGen CA192682504, ClinVar RCV000736269, TOPMed rs866101707, REVEL 0.75, CADD 27.60, Likely pathogenic, Alzheimer disease
- E141A (p.Glu141Ala), Ensembl rs2131038903
- E141K (p.Glu141Lys), NCI-TCGA Cosmic COSV6272, Variant assessed as somatic; moderate impact.
- A142V (p.Ala142Val), NCI-TCGA Cosmic COSV6271, Variant assessed as somatic; moderate impact.
- R144* (p.Arg144Ter), NCI-TCGA Cosmic COSV6272, Variant assessed as somatic; high impact.
- R144Q (p.Arg144Gln), gnomAD rs866582683, REVEL 0.90, CADD 29.90
- I146V (p.Ile146Val), Ensembl rs1828839805
- R147W (p.Arg147Trp), TOPMed rs1315819281
- G149A (p.Gly149Ala), NCI-TCGA Cosmic COSV6272, Variant assessed as somatic; moderate impact.
- G149R (p.Gly149Arg), ExAC rs775948048, gnomAD rs775948048
- I151M (p.Ile151Met), rs1828808459, ClinGen CA373289743, ClinVar RCV001212890, Ensembl rs1828808459, AlphaMissense 0.12, MetaLR 0.81, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- I151V (p.Ile151Val), rs367881889, ClinGen CA192681647, ClinVar RCV001890377, ClinVar RCV003355609, REVEL 0.40, CADD 20.40, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- F152L (p.Phe152Leu), TOPMed rs1828808389
- V154F (p.Val154Phe), rs1587127201, ClinGen CA373289681, ClinVar RCV001312665, gnomAD rs1587127201, AlphaMissense 0.97, MetaLR 0.97, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- V154I (p.Val154Ile), gnomAD rs1587127201, REVEL 0.47, AlphaMissense 0.97, Uncertain significance
- R155C (p.Arg155Cys), rs121909330, ClinGen CA254398, NCI-TCGA Cosmic COSV1007, NCI-TCGA Cosmic COSV6271, AlphaMissense 0.95, MetaLR 0.95, Pathogenic/Likely pathogenic, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- R155G (p.Arg155Gly), rs121909330, ClinGen CA277489, ClinVar RCV000196145, ClinVar RCV000494556, AlphaMissense 0.95, MetaLR 0.95, Pathogenic/Likely pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- R155H (p.Arg155His), rs121909329, ClinGen CA128983, ClinVar RCV000008989, ClinVar RCV000523065, REVEL 0.73, AlphaMissense 0.97, Pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- R155L (p.Arg155Leu), rs121909329, UniProt VAR 078910, Ensembl rs121909329, AlphaMissense 0.97, MetaLR 0.91, Pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- R155P (p.Arg155Pro), rs121909329, ClinGen CA254404, ClinVar RCV000008993, ClinVar RCV001387337, AlphaMissense 0.97, MetaLR 0.91, Conflicting interpretations, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- R155S (p.Arg155Ser), rs121909330, ClinGen CA373289661, ClinVar RCV001949225, UniProt VAR 076466, AlphaMissense 0.95, MetaLR 0.95, Pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- G156S (p.Gly156Ser), rs1554668817, ClinGen CA373289624, ClinVar RCV003037322, ClinVar RCV005227805, AlphaMissense 0.66, MetaLR 0.89, Pathogenic/Likely pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- G156V (p.Gly156Val), rs2490366443, ClinGen CA373289611, ClinVar RCV003803471, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- G157R (p.Gly157Arg), rs1554668814, ClinGen CA373289608, ClinVar RCV001972632, Ensembl rs1554668814, AlphaMissense 0.99, MetaLR 0.94, Pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- G157W (p.Gly157Trp), Ensembl rs1554668814, Pathogenic
- M158T (p.Met158Thr), Ensembl rs1828807231
- M158V (p.Met158Val), rs1554668813, ClinGen CA373289580, ClinVar RCV001953725, Ensembl rs1554668813, AlphaMissense 0.77, MetaLR 0.92, Pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- R159C (p.Arg159Cys), rs387906789, ClinGen CA5039453, ClinVar RCV000333881, ClinVar RCV001095425, REVEL 0.94, AlphaMissense 0.96, Pathogenic/Likely pathogenic, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- R159G (p.Arg159Gly), rs387906789, ClinGen CA259748, ClinVar RCV000023065, UniProt VAR 065910, AlphaMissense 0.96, MetaLR 0.96, Pathogenic, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- R159H (p.Arg159His), rs121909335, ClinGen CA254408, ClinVar RCV000008995, ClinVar RCV000276565, REVEL 0.60, CADD 23.20, Pathogenic, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- R159S (p.Arg159Ser), rs387906789, ClinGen CA373289529, ClinVar RCV001271083, ClinVar RCV006279524, AlphaMissense 0.96, MetaLR 0.96, Likely pathogenic, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- A160P (p.Ala160Pro), rs1554668805, ClinGen CA373289512, ClinVar RCV000639654, ClinVar RCV000993545, AlphaMissense 0.48, MetaLR 0.81, Conflicting interpretations, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- A160T (p.Ala160Thr), rs1554668805, ClinGen CA373289514, ClinVar RCV003139268, UniProt VAR 088265, AlphaMissense 0.48, MetaLR 0.81, Likely pathogenic, not provided
- A160V (p.Ala160Val), rs1554668804, ClinGen CA373289480, ClinVar RCV002233477, Ensembl rs1554668804, AlphaMissense 0.74, MetaLR 0.87, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- E162D (p.Glu162Asp), rs2490366398, ClinGen CA373289436, ClinVar RCV003019916, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- F163I (p.Phe163Ile), rs2490366389, ClinGen CA373289413, ClinVar RCV003807372, REVEL 0.91, CADD 29.10, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- V165A (p.Val165Ala), TOPMed rs974794063
- V165M (p.Val165Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S171I (p.Ser171Ile), rs200911363, ClinGen CA5039451, ClinVar RCV000793063, 1000Genomes rs200911363, REVEL 0.56, CADD 22.60, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- S171N (p.Ser171Asn), rs200911363, ClinGen CA5039452, ClinVar RCV001361941, 1000Genomes rs200911363, REVEL 0.33, CADD 22.40, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- S171R (p.Ser171Arg), rs2131036685, ClinGen CA373289239, ClinVar RCV001541190, Ensembl rs2131036685, AlphaMissense 0.89, MetaLR 0.80, Uncertain significance, not provided
- P172L (p.Pro172Leu), NCI-TCGA Cosmic COSV6272, Variant assessed as somatic; moderate impact.
- Y173C (p.Tyr173Cys), ExAC rs766261105, gnomAD rs766261105
- Y173H (p.Tyr173His), Ensembl rs1587127096
- I175T (p.Ile175Thr), Ensembl rs1828805958, REVEL 0.89, CADD 27.40, Uncertain significance, VCP-related disorder
- I175V (p.Ile175Val), rs1828806031, ClinGen CA373289133, ClinVar RCV001212543, Ensembl rs1828806031, AlphaMissense 0.35, MetaLR 0.74, Uncertain significance, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- V181L (p.Val181Leu), gnomAD rs1275676999, REVEL 0.41, CADD 22.10
- H183Y (p.His183Tyr), NCI-TCGA Cosmic COSV6272, Variant assessed as somatic; moderate impact.
- E185D (p.Glu185Asp), rs1333833979, ClinGen CA373288786, ClinVar RCV000730388, ClinVar RCV005223150, REVEL 0.51, CADD 17.50, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
- E185K (p.Glu185Lys), rs864309501, ClinGen CA213386, ClinVar RCV000202444, ClinVar RCV002229147, REVEL 0.92, CADD 25.00, Likely pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
- P188H (p.Pro188His), gnomAD rs1410410076, Likely pathogenic, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia t
- P188L (p.Pro188Leu), rs1410410076, ClinGen CA373288731, ClinVar RCV003994618, REVEL 0.76, CADD 31.00, Uncertain significance, Inclusion body myopathy with Paget disease of bone and frontotemporal dementia t
- P188R (p.Pro188Arg), gnomAD rs1410410076
- P188S (p.Pro188Ser), gnomAD rs1309590903, REVEL 0.77, CADD 28.10
- I189V (p.Ile189Val), rs747754993, ClinGen CA5039446, ClinVar RCV003100354, ClinVar RCV004697252, REVEL 0.31, CADD 19.80, Uncertain significance, not provided; Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; In
- K190R (p.Lys190Arg), ExAC rs776154559, TOPMed rs776154559, gnomAD rs776154559, REVEL 0.32, CADD 22.90
- R191P (p.Arg191Pro), rs121909334, ClinGen CA373288667, ClinVar RCV001095426, ClinVar RCV003769035, AlphaMissense 0.96, MetaLR 0.96, Pathogenic/Likely pathogenic, Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body m
Public VCP analysis runs
- VCP analysis run — VCP (792 variants) — completed 2026-08-19