Is GCOM1 p.Val367Ile (c.1099G>A) pathogenic?

GCOM1 p.Val367Ile (c.1099G>A) is classified Uncertain significance in GCOM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.2763); Rare (popmax 0.132%, mid); Associated with Inborn genetic diseases.

What condition is associated with GCOM1 p.Val367Ile (c.1099G>A)?

GCOM1 p.Val367Ile (c.1099G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GCOM1 p.Val367Ile (c.1099G>A) in the general population?

GCOM1 p.Val367Ile (c.1099G>A) is rare (popmax 0.132%, mid) (gnomAD).

What do computational predictors say about GCOM1 p.Val367Ile (c.1099G>A)?

AlphaMissense predicts likely benign (score 0.2763) — an in-silico prediction, not a clinical call.

GCOM1 p.Val367Ile

c.1099G>A · VCV4262687

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2763 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2763	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -4.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 6.9, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 92 kb · p 0.02 · regional, not allelic
Overall
CADD	27.4	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 0.132% Middle Eastern · 8/6,050 alleles

Filtering AF 0.0829% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0761%

Overall 0.0232% 374/1,614,010 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	756
African / African-American	0.101%	988
Admixed American	0.0483%	2,070
Remaining individualsnot grpmax-eligible	0.0368%	2,717
European (non-Finnish)	0.0198%	5,043
South Asian	0.00439%	22,762

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: GCOM1
Protein: p.Val367Ile
Coding: c.1099G>A
MANE Select: NM_001018100 · reported on NM_001018090
Type: single nucleotide variant
Location: chr15:57639525 (GRCh38)

Full GCOM1 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

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/gcom1-p-val367ile (accessed [today's date]).

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