Is VCP p.Phe131Ser (c.392T>C) pathogenic?

VCP p.Phe131Ser (c.392T>C) is classified Uncertain significance in VCP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-27). AlphaMissense: likely pathogenic (0.9782); Absent from gnomAD v4.1.

How common is VCP p.Phe131Ser (c.392T>C) in the general population?

VCP p.Phe131Ser (c.392T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VCP p.Phe131Ser (c.392T>C)?

AlphaMissense predicts likely pathogenic (score 0.9782) — an in-silico prediction, not a clinical call.

VCP p.Phe131Ser

c.392T>C · rs2490370305 · VCV2438517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9782 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9782	likely pathogenic
REVEL	0.94	strongly pathogenic-leaning
SaProt	LLR -16.34	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.25	constrained · MANE · 5,151 bp · p 1.5e-44 · regional, not allelic
Overall
CADD	32.0	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.Phe131Ser
Coding: c.392T>C
MANE Select: NM_007126
dbSNP: rs2490370305
Type: single nucleotide variant
Location: chr9:35066728 (GRCh38)
Gene constraint: LOEUF 0.134 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.11 · 144 PDB
Residue 131: an α-helix

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

Similar variants

VCP p.Phe131= Likely benign ★ same residue
VCP p.Arg155Cys Pathogenic/Likely pathogenic ★★ same type
VCP p.Arg155Gly Pathogenic/Likely pathogenic ★★ same type
VCP p.Arg155His Pathogenic ★★ ⚠ same type
VCP p.Arg159Cys Pathogenic/Likely pathogenic ★★ same type
VCP p.Arg159His Pathogenic ★★ same type
VCP p.Arg191Gln Pathogenic/Likely pathogenic ★★ same type
VCP p.Arg191Pro Pathogenic/Likely pathogenic ★★ same type

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-phe131ser (accessed [today's date]).

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