Is OMD p.Met227Val (c.679A>G) pathogenic?

OMD p.Met227Val (c.679A>G) is classified Uncertain significance in OMD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: likely benign (0.1606); Very rare (popmax 0.000847%, nfe).

How common is OMD p.Met227Val (c.679A>G) in the general population?

OMD p.Met227Val (c.679A>G) is very rare (popmax 0.000847%, nfe) (gnomAD).

What do computational predictors say about OMD p.Met227Val (c.679A>G)?

AlphaMissense predicts likely benign (score 0.1606) — an in-silico prediction, not a clinical call.

OMD p.Met227Val

c.679A>G · VCV3882762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1606	likely benign
REVEL	0.205	benign-leaning
SaProt	LLR -5.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,403 bp · p 0.054 · regional, not allelic
Overall
CADD	23.9	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 0.000847% European (non-Finnish) · 10/1,179,966 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.00062% 10/1,613,914 alleles · very rare

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.Met227Val
Coding: c.679A>G
MANE Select: NM_001012267 · reported on NM_005014
Type: single nucleotide variant
Location: chr9:92416880 (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-met227val (accessed [today's date]).

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