Is OMD p.Pro90Leu (c.269C>T) pathogenic?

OMD p.Pro90Leu (c.269C>T) is classified Uncertain significance in OMD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-04). AlphaMissense: likely pathogenic (0.6593); Ultra-rare (popmax 0.0134%, eas).

How common is OMD p.Pro90Leu (c.269C>T) in the general population?

OMD p.Pro90Leu (c.269C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about OMD p.Pro90Leu (c.269C>T)?

AlphaMissense predicts likely pathogenic (score 0.6593) — an in-silico prediction, not a clinical call.

OMD p.Pro90Leu

c.269C>T · rs142713990 · VCV2356123

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6593 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6593	likely pathogenic
REVEL	0.917	moderately pathogenic-leaning
SaProt	LLR -6.92	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 8.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,403 bp · p 0.054 · regional, not allelic
Overall
CADD	26.0	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 0.0134% East Asian · 6/44,872 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00124% 20/1,613,914 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,479
African / African-American	0.00534%	18,726
South Asian	0.0022%	45,542
Admixed American	0.00167%	59,992
European (non-Finnish)	0.000593%	168,569

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: OMD
Protein: p.Pro90Leu
Coding: c.269C>T
MANE Select: NM_001012267 · reported on NM_005014
dbSNP: rs142713990
Type: single nucleotide variant
Location: chr9:92417290 (GRCh38)

Full OMD 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/omd-p-pro90leu (accessed [today's date]).

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