Is VCP p.Ile643= (c.1929C>T) pathogenic?

VCP p.Ile643= (c.1929C>T) is classified Conflicting classifications of pathogenicity in VCP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-02-03). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

How common is VCP p.Ile643= (c.1929C>T) in the general population?

VCP p.Ile643= (c.1929C>T) is absent from gnomAD v4.1 (gnomAD).

VCP p.Ile643=

Q: What condition is associated with VCP p.Ile643= (c.1929C>T)?

VCP p.Ile643= (c.1929C>T) is associated with Inborn genetic diseases, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (ClinVar).

c.1929C>T · rs1554668168 · VCV502139

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3	GERP -1.2, phastCons 1
Overall
CADD	8.637	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: VCP
Protein: p.Ile643=
Coding: c.1929C>T
MANE Select: NM_007126
dbSNP: rs1554668168
Type: single nucleotide variant
Location: chr9:35059568 (GRCh38)
Gene constraint: LOEUF 0.134 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.11 · 144 PDB
Residue 643: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inclusion body myopathy with Paget disease of bone and frontotemporal dementia frontotemporal dementia and/or amyotrophic lateral sclerosis 6

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-ile643 (accessed [today's date]).

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