Is ERMN p.Met282Val (c.844A>G) pathogenic?

ERMN p.Met282Val (c.844A>G) is classified Uncertain significance in ERMN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-10). AlphaMissense: ambiguous (0.4812); Ultra-rare (popmax 0.0147%, afr).

How common is ERMN p.Met282Val (c.844A>G) in the general population?

ERMN p.Met282Val (c.844A>G) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about ERMN p.Met282Val (c.844A>G)?

AlphaMissense predicts ambiguous (score 0.4812) — an in-silico prediction, not a clinical call.

ERMN p.Met282Val

c.844A>G · VCV3846120

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4812 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4812	ambiguous
REVEL	0.194	benign-leaning
SaProt	LLR -8.29	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 2.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 4,368 bp · p 0.37 · regional, not allelic
Overall
CADD	20.6	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 0.0147% African / African-American · 11/74,892 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000682% 11/1,612,946 alleles · ultra-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: ERMN
Protein: p.Met282Val
Coding: c.844A>G
MANE Select: NM_020711
Type: single nucleotide variant
Location: chr2:157321282 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.95
Residue 282: the 'binds actin' region

Full ERMN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERMN p.Ala52Thr Benign ★★ same type
ERMN c.-27T>G Uncertain significance ★ same type
ERMN p.Ala11Asp Uncertain significance ★ ⚠ same type
ERMN p.Ala93Pro Uncertain significance ★ ⚠ same type
ERMN p.Arg110Gly Uncertain significance ★ ⚠ same type
ERMN p.Arg128Gly Uncertain significance ★ ⚠ same type
ERMN p.Arg147Gly Uncertain significance ★ ⚠ same type
ERMN p.Arg163Leu Uncertain significance ★ ⚠ same type

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/ermn-p-met282val (accessed [today's date]).

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