Is GCOM1 p.Gln175Pro (c.524A>C) pathogenic?

GCOM1 p.Gln175Pro (c.524A>C) is classified Uncertain significance in GCOM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-11). AlphaMissense: likely pathogenic (0.8878); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GCOM1 p.Gln175Pro (c.524A>C)?

GCOM1 p.Gln175Pro (c.524A>C) is associated with Inborn genetic diseases (ClinVar).

How common is GCOM1 p.Gln175Pro (c.524A>C) in the general population?

GCOM1 p.Gln175Pro (c.524A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GCOM1 p.Gln175Pro (c.524A>C)?

AlphaMissense predicts likely pathogenic (score 0.8878) — an in-silico prediction, not a clinical call.

GCOM1 p.Gln175Pro

c.524A>C · VCV3853299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8878 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8878	likely pathogenic
REVEL	0.491	indeterminate
SaProt	LLR -13.43	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.53	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 92 kb · p 0.02 · regional, not allelic
Overall
CADD	28.8	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: GCOM1
Protein: p.Gln175Pro
Coding: c.524A>C
Type: single nucleotide variant
Location: chr15:57625891 (GRCh38)
Gene constraint: LOEUF 1.129 · pLI <0.01 (gnomAD)

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

Similar variants

GCOM1 p.Ala109Thr Uncertain significance ★ ⚠ same condition
GCOM1 p.Ala168Val Uncertain significance ★ ⚠ same condition
GCOM1 p.Ala16Val Uncertain significance ★ ⚠ same condition
GCOM1 p.Ala288Thr Uncertain significance ★ ⚠ same condition
GCOM1 p.Ala345Ser Uncertain significance ★ ⚠ same condition
GCOM1 p.Arg108Thr Uncertain significance ★ ⚠ same condition
GCOM1 p.Arg117Gln Uncertain significance ★ ⚠ same condition
GCOM1 p.Arg130Leu 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/gcom1-p-gln175pro (accessed [today's date]).

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