Is GCOM1 p.Gln83Pro (c.248A>C) pathogenic?

GCOM1 p.Gln83Pro (c.248A>C) is classified Uncertain significance in GCOM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.1408); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GCOM1 p.Gln83Pro (c.248A>C)?

GCOM1 p.Gln83Pro (c.248A>C) is associated with Inborn genetic diseases (ClinVar).

How common is GCOM1 p.Gln83Pro (c.248A>C) in the general population?

GCOM1 p.Gln83Pro (c.248A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GCOM1 p.Gln83Pro (c.248A>C)?

AlphaMissense predicts likely benign (score 0.1408) — an in-silico prediction, not a clinical call.

GCOM1 p.Gln83Pro

c.248A>C · rs2551695855 · VCV2240048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1408 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1408	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -5.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 92 kb · p 0.02 · regional, not allelic
Overall
CADD	25.0	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

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.Gln83Pro
Coding: c.248A>C
dbSNP: rs2551695855
Type: single nucleotide variant
Location: chr15:57618118 (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-gln83pro (accessed [today's date]).

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