Is GCOM1 p.Ala16Val (c.47C>T) pathogenic?

GCOM1 p.Ala16Val (c.47C>T) is classified Uncertain significance in GCOM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-20). AlphaMissense: likely benign (0.1234); Ultra-rare (popmax 0.0107%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GCOM1 p.Ala16Val (c.47C>T)?

GCOM1 p.Ala16Val (c.47C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GCOM1 p.Ala16Val (c.47C>T) in the general population?

GCOM1 p.Ala16Val (c.47C>T) is ultra-rare (popmax 0.0107%, nfe) (gnomAD).

What do computational predictors say about GCOM1 p.Ala16Val (c.47C>T)?

AlphaMissense predicts likely benign (score 0.1234) — an in-silico prediction, not a clinical call.

GCOM1 p.Ala16Val

c.47C>T · VCV3281079

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1234 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1234	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.42	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 1.7	GERP 6.1, phastCons 0.1
Regional constraint	o/e 1.10	unconstrained · MANE · 92 kb · p 0.02 · regional, not allelic
Overall
CADD	18.35	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 0.0107% European (non-Finnish) · 115/1,071,184 alleles

Filtering AF 0.0091% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00852%

Overall 0.00862% 119/1,380,348 alleles · ultra-rare exomes 106/1,228,118 · genomes 13/152,230 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0107%	9,315
Admixed American	0.0068%	14,702
Remaining individualsnot grpmax-eligible	0.00385%	25,977

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.Ala16Val
Coding: c.47C>T
Type: single nucleotide variant
Location: chr15:57592081 (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.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
GCOM1 p.Arg130Pro 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-ala16val (accessed [today's date]).

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