Is VCP p.Ser784Arg (c.2352T>G) pathogenic?

VCP p.Ser784Arg (c.2352T>G) is classified Uncertain significance in VCP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). AlphaMissense: likely pathogenic (0.8138); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with VCP p.Ser784Arg (c.2352T>G)?

VCP p.Ser784Arg (c.2352T>G) is associated with Inborn genetic diseases (ClinVar).

How common is VCP p.Ser784Arg (c.2352T>G) in the general population?

VCP p.Ser784Arg (c.2352T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VCP p.Ser784Arg (c.2352T>G)?

AlphaMissense predicts likely pathogenic (score 0.8138) — an in-silico prediction, not a clinical call.

VCP p.Ser784Arg

c.2352T>G · rs2490338894 · VCV2556908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8138 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8138	likely pathogenic
REVEL	0.405	indeterminate
SaProt	LLR -10.84	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.59, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 2,398 bp · p 1.2e-13 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ser784Arg
Coding: c.2352T>G
MANE Select: NM_007126
dbSNP: rs2490338894
Type: single nucleotide variant
Location: chr9:35057186 (GRCh38)
Gene constraint: LOEUF 0.134 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.11 · 144 PDB
Residue 784: the 'disordered' region

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

Similar variants

VCP c.811+2T>C Uncertain significance ★★ same condition
VCP p.Ala31Ser Uncertain significance ★★ ⚠ same condition
VCP p.Arg711Gln Uncertain significance ★★ ⚠ same condition
VCP p.Asn443His Uncertain significance ★★ same condition
VCP p.Ile540Val Uncertain significance ★★ ⚠ same condition
VCP p.Lys277Arg Uncertain significance ★★ ⚠ same condition
VCP p.Lys658Glu Uncertain significance ★★ ⚠ same condition
VCP p.Lys658Thr Uncertain significance ★★ ⚠ 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-ser784arg (accessed [today's date]).

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