Is GCOM1 p.Pro434Arg (c.1301C>G) pathogenic?

GCOM1 p.Pro434Arg (c.1301C>G) is classified Uncertain significance in GCOM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely benign (0.1545); Ultra-rare (popmax 0.0332%, mid); Associated with Inborn genetic diseases.

What condition is associated with GCOM1 p.Pro434Arg (c.1301C>G)?

GCOM1 p.Pro434Arg (c.1301C>G) is associated with Inborn genetic diseases (ClinVar).

How common is GCOM1 p.Pro434Arg (c.1301C>G) in the general population?

GCOM1 p.Pro434Arg (c.1301C>G) is ultra-rare (popmax 0.0332%, mid) (gnomAD).

What do computational predictors say about GCOM1 p.Pro434Arg (c.1301C>G)?

AlphaMissense predicts likely benign (score 0.1545) — an in-silico prediction, not a clinical call.

GCOM1 p.Pro434Arg

c.1301C>G · rs771603160 · VCV3099151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1545 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0332%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1545	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -7.24	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 4.1	GERP 7.2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 92 kb · p 0.02 · regional, not allelic
Overall
CADD	24.6	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 0.0332% Middle Eastern · 2/6,024 alleles

Filtering AF 0.00585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.00113% 18/1,599,770 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0332%	3,012
Remaining individualsnot grpmax-eligible	0.00645%	15,510
European (non-Finnish)	0.00102%	97,960

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.Pro434Arg
Coding: c.1301C>G
dbSNP: rs771603160
Type: single nucleotide variant
Location: chr15:57675065 (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-pro434arg (accessed [today's date]).

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