Is OMP p.Val16Leu (c.46G>C) pathogenic?

OMP p.Val16Leu (c.46G>C) is classified Uncertain significance in OMP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-30). AlphaMissense: likely benign (0.1218); Ultra-rare (popmax 0.0527%, nfe).

How common is OMP p.Val16Leu (c.46G>C) in the general population?

OMP p.Val16Leu (c.46G>C) is ultra-rare (popmax 0.0527%, nfe) (gnomAD).

What do computational predictors say about OMP p.Val16Leu (c.46G>C)?

AlphaMissense predicts likely benign (score 0.1218) — an in-silico prediction, not a clinical call.

OMP p.Val16Leu

c.46G>C · rs200579402 · VCV2358676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1218 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0527%, nfe)

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	0.1218	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.5	GERP 1.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 488 bp · p 0.42 · regional, not allelic
Overall
CADD	19.37	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 0.0527% European (non-Finnish) · 622/1,179,650 alleles

Filtering AF 0.0492% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0479%

Overall 0.0409% 659/1,611,618 alleles · ultra-rare exomes 614/1,459,358 · genomes 45/152,260 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0527%	1,897
Admixed American	0.0267%	3,748
Remaining individualsnot grpmax-eligible	0.0192%	5,197
Finnishnot grpmax-eligible	0.00799%	12,517
African / African-American	0.00534%	18,730

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.Val16Leu
Coding: c.46G>C
MANE Select: NM_006189
dbSNP: rs200579402
Type: single nucleotide variant
Location: chr11:77102885 (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-val16leu (accessed [today's date]).

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