Is OMP p.Leu91Phe (c.271C>T) pathogenic?

OMP p.Leu91Phe (c.271C>T) is classified Uncertain significance in OMP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely pathogenic (0.6509); Ultra-rare (popmax 0.02%, eas).

How common is OMP p.Leu91Phe (c.271C>T) in the general population?

OMP p.Leu91Phe (c.271C>T) is ultra-rare (popmax 0.02%, eas) (gnomAD).

What do computational predictors say about OMP p.Leu91Phe (c.271C>T)?

AlphaMissense predicts likely pathogenic (score 0.6509) — an in-silico prediction, not a clinical call.

OMP p.Leu91Phe

c.271C>T · rs782570316 · VCV2402872

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6509 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL 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	0.6509	likely pathogenic
REVEL	0.597	indeterminate
SaProt	LLR -9.27	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 488 bp · p 0.42 · regional, not allelic
Overall
CADD	25.1	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 0.02% East Asian · 9/44,896 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.000929% 15/1,613,770 alleles · ultra-rare exomes 10/1,461,558 · genomes 5/152,212 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	4,988
South Asian	0.0011%	91,086
European (non-Finnish)	0.000424%	235,978

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.Leu91Phe
Coding: c.271C>T
MANE Select: NM_006189
dbSNP: rs782570316
Type: single nucleotide variant
Location: chr11:77103110 (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-leu91phe (accessed [today's date]).

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