Is OMP p.Val158Met (c.472G>A) pathogenic?

OMP p.Val158Met (c.472G>A) is classified Uncertain significance in OMP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). AlphaMissense: ambiguous (0.3684); Ultra-rare (popmax 0.0165%, mid).

How common is OMP p.Val158Met (c.472G>A) in the general population?

OMP p.Val158Met (c.472G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about OMP p.Val158Met (c.472G>A)?

AlphaMissense predicts ambiguous (score 0.3684) — an in-silico prediction, not a clinical call.

OMP p.Val158Met

c.472G>A · rs781913420 · VCV3204313

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3684 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

⚠ 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	0.3684	ambiguous
REVEL	0.182	moderately benign-leaning
SaProt	LLR -8.84	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 8.4	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 488 bp · p 0.42 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,054 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000993% 16/1,610,528 alleles · ultra-rare exomes 11/1,458,252 · genomes 5/152,276 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,054
Remaining individualsnot grpmax-eligible	0.00321%	31,200
South Asian	0.0022%	45,527
Finnishnot grpmax-eligible	0.0016%	62,560
African / African-American	0.00133%	75,010
European (non-Finnish)	0.000764%	130,907

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.Val158Met
Coding: c.472G>A
MANE Select: NM_006189
dbSNP: rs781913420
Type: single nucleotide variant
Location: chr11:77103311 (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-val158met (accessed [today's date]).

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