Is VCP p.Ser3= (c.9T>C) pathogenic?

VCP p.Ser3= (c.9T>C) is classified Likely benign in VCP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-24). Very rare (popmax 0.000888%, nfe); Associated with inclusion body myopathy with Paget disease of bone and frontotemporal dementia.

What condition is associated with VCP p.Ser3= (c.9T>C)?

VCP p.Ser3= (c.9T>C) is associated with inclusion body myopathy with Paget disease of bone and frontotemporal dementia, frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (ClinVar).

How common is VCP p.Ser3= (c.9T>C) in the general population?

VCP p.Ser3= (c.9T>C) is very rare (popmax 0.000888%, nfe) (gnomAD).

VCP p.Ser3=

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.9T>C · rs1782639546 · VCV2930746

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000888%, nfe)

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 -0.26	GERP -1.2, phastCons 0.011
Overall
CADD	13.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000888% European (non-Finnish) · 10/1,125,994 alleles

Filtering AF 0.000449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000327%

Overall 0.00075% 10/1,334,198 alleles · very rare

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.Ser3=
Coding: c.9T>C
MANE Select: NM_007126
dbSNP: rs1782639546
Type: single nucleotide variant
Location: chr9:35072345 (GRCh38)
Gene constraint: LOEUF 0.134 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.11 · 144 PDB
Residue 3: a modified residue (phosphoserine)

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-ser3 (accessed [today's date]).

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