Is OMP p.Ala49Glu (c.146C>A) pathogenic?

OMP p.Ala49Glu (c.146C>A) is classified Uncertain significance in OMP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-04). AlphaMissense: likely benign (0.1463); Very rare (popmax 0.00167%, amr).

How common is OMP p.Ala49Glu (c.146C>A) in the general population?

OMP p.Ala49Glu (c.146C>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about OMP p.Ala49Glu (c.146C>A)?

AlphaMissense predicts likely benign (score 0.1463) — an in-silico prediction, not a clinical call.

OMP p.Ala49Glu

c.146C>A · VCV3924141

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1463 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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	0.1463	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -5.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.1	GERP 0.69
Regional constraint	o/e 1.05	unconstrained · MANE · 488 bp · p 0.42 · regional, not allelic
Overall
CADD	13.89	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 0.00167% Admixed American · 1/60,002 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00118% 19/1,613,290 alleles · very rare exomes 16/1,461,060 · genomes 3/152,230 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
European (non-Finnish)	0.00144%	69,407
African / African-American	0.00133%	74,936

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.Ala49Glu
Coding: c.146C>A
MANE Select: NM_006189
Type: single nucleotide variant
Location: chr11:77102985 (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-ala49glu (accessed [today's date]).

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