Is OMP p.Ala2Val (c.5C>T) pathogenic?

OMP p.Ala2Val (c.5C>T) is classified Uncertain significance in OMP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). AlphaMissense: likely benign (0.2029); Ultra-rare (popmax 0.0411%, mid).

How common is OMP p.Ala2Val (c.5C>T) in the general population?

OMP p.Ala2Val (c.5C>T) is ultra-rare (popmax 0.0411%, mid) (gnomAD).

What do computational predictors say about OMP p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely benign (score 0.2029) — an in-silico prediction, not a clinical call.

OMP p.Ala2Val

c.5C>T · VCV4125588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2029 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0411%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2029	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -7.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 488 bp · p 0.42 · regional, not allelic
Overall
CADD	21.0	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

Grpmax group 0.0411% Middle Eastern · 2/4,864 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00301%

Overall 0.00114% 18/1,585,302 alleles · ultra-rare exomes 16/1,432,918 · genomes 2/152,384 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0411%	2,432
Remaining individualsnot grpmax-eligible	0.00489%	20,431
South Asian	0.00342%	29,251
East Asian	0.00227%	43,986
African / African-American	0.00134%	74,580
European (non-Finnish)	0.000685%	145,888

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: OMP
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_006189
Type: single nucleotide variant
Location: chr11:77102844 (GRCh38)

Full OMP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/omp-p-ala2val (accessed [today's date]).

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