Is VCP p.Pro350= (c.1050C>G) pathogenic?

VCP p.Pro350= (c.1050C>G) is classified Likely benign in VCP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-18). Very rare (popmax 0.00333%, amr); Associated with inclusion body myopathy with Paget disease of bone and frontotemporal dementia.

How common is VCP p.Pro350= (c.1050C>G) in the general population?

VCP p.Pro350= (c.1050C>G) is very rare (popmax 0.00333%, amr) (gnomAD).

VCP p.Pro350=

Q: What condition is associated with VCP p.Pro350= (c.1050C>G)?

VCP p.Pro350= (c.1050C>G) is associated with inclusion body myopathy with Paget disease of bone and frontotemporal dementia, frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (ClinVar).

Q: How is Inclusion body myopathy with Paget disease of bone and frontotemporal dementia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1050C>G · rs753103789 · VCV2173273

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

inclusion body myopathy with Paget disease of bone and frontotemporal dementia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -2.2, phastCons 1
Overall
CADD	7.603	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,020 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,614,164 alleles · very rare exomes 2/1,461,892 · genomes 0/152,272 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: VCP
Protein: p.Pro350=
Coding: c.1050C>G
MANE Select: NM_007126
dbSNP: rs753103789
Type: single nucleotide variant
Location: chr9:35062034 (GRCh38)
Gene constraint: LOEUF 0.134 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.11 · 144 PDB
Residue 350: an α-helix

Full VCP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inclusion body myopathy with Paget disease of bone and frontotemporal dementia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: frontotemporal dementia and/or amyotrophic lateral sclerosis 6

For Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

VCP p.Arg155Cys Pathogenic/Likely pathogenic ★★ same condition
VCP p.Arg155Gly Pathogenic/Likely pathogenic ★★ same condition
VCP p.Arg155His Pathogenic ★★ ⚠ same condition
VCP p.Arg159Cys Pathogenic/Likely pathogenic ★★ same condition
VCP p.Arg159His Pathogenic ★★ same condition
VCP p.Arg191Gln Pathogenic/Likely pathogenic ★★ same condition
VCP p.Arg191Pro Pathogenic/Likely pathogenic ★★ same condition
VCP p.Arg256Gly Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/vcp-p-pro350 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown