Is VCP p.Val367Ile (c.1099G>A) pathogenic?

VCP p.Val367Ile (c.1099G>A) is classified Uncertain significance in VCP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.0851); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with VCP p.Val367Ile (c.1099G>A)?

VCP p.Val367Ile (c.1099G>A) is associated with Inborn genetic diseases (ClinVar).

How common is VCP p.Val367Ile (c.1099G>A) in the general population?

VCP p.Val367Ile (c.1099G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about VCP p.Val367Ile (c.1099G>A)?

AlphaMissense predicts likely benign (score 0.0851) — an in-silico prediction, not a clinical call.

VCP p.Val367Ile

c.1099G>A · VCV4198561

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0851 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0851	likely benign
REVEL	0.398	indeterminate
SaProt	LLR -1.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	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	19.94	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,978 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,870 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.Val367Ile
Coding: c.1099G>A
MANE Select: NM_007126
Type: single nucleotide variant
Location: chr9:35061672 (GRCh38)
Gene constraint: LOEUF 0.134 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.11 · 144 PDB
Residue 367: 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

Similar variants

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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-val367ile (accessed [today's date]).

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