Is OMP p.Leu163Pro (c.488T>C) pathogenic?

OMP p.Leu163Pro (c.488T>C) is classified Uncertain significance in OMP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: ambiguous (0.4192); Ultra-rare (popmax 0.0629%, afr).

How common is OMP p.Leu163Pro (c.488T>C) in the general population?

OMP p.Leu163Pro (c.488T>C) is ultra-rare (popmax 0.0629%, afr) (gnomAD).

What do computational predictors say about OMP p.Leu163Pro (c.488T>C)?

AlphaMissense predicts ambiguous (score 0.4192) — an in-silico prediction, not a clinical call.

OMP p.Leu163Pro

c.488T>C · rs373423261 · VCV2265753

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4192 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0629%, afr)

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	0.4192	ambiguous
REVEL	0.221	benign-leaning
SaProt	LLR -5.59	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 6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 488 bp · p 0.42 · regional, not allelic
Overall
CADD	24.3	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 0.0629% African / African-American · 47/74,732 alleles

Filtering AF 0.0485% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0435%

Overall 0.00324% 52/1,605,846 alleles · ultra-rare exomes 32/1,453,730 · genomes 20/152,116 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0629%	1,590
Middle Eastern	0.0165%	6,068
Remaining individualsnot grpmax-eligible	0.00322%	31,070
Admixed American	0.00167%	59,748
South Asian	0.0011%	90,918

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.Leu163Pro
Coding: c.488T>C
MANE Select: NM_006189
dbSNP: rs373423261
Type: single nucleotide variant
Location: chr11:77103327 (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-leu163pro (accessed [today's date]).

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