Is EID2 p.Met63Ile (c.189G>A) pathogenic?

EID2 p.Met63Ile (c.189G>A) is classified Uncertain significance in EID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: ambiguous (0.4057); Very rare (popmax 0.00251%, nfe).

How common is EID2 p.Met63Ile (c.189G>A) in the general population?

EID2 p.Met63Ile (c.189G>A) is very rare (popmax 0.00251%, nfe) (gnomAD).

What do computational predictors say about EID2 p.Met63Ile (c.189G>A)?

AlphaMissense predicts ambiguous (score 0.4057) — an in-silico prediction, not a clinical call.

EID2 p.Met63Ile

c.189G>A · rs1011075161 · VCV3087830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4057 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00251%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4057	ambiguous
REVEL	0.076	moderately benign-leaning
SaProt	LLR -7.63	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 -0.34	GERP 0.65
Regional constraint	o/e 0.84	unconstrained · MANE · 707 bp · p 0.0037 · regional, not allelic
Overall
CADD	5.14	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 0.00251% European (non-Finnish) · 27/1,075,832 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00147%

Overall 0.00201% 28/1,392,516 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00251%	39,846
Remaining individualsnot grpmax-eligible	0.00188%	53,182

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: EID2
Protein: p.Met63Ile
Coding: c.189G>A
MANE Select: NM_153232
dbSNP: rs1011075161
Type: single nucleotide variant
Location: chr19:39539891 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI 0.43 (gnomAD)
Structure: AlphaFold pLDDT 58.28
Residue 63: the 'disordered' region

Full EID2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EID2 p.Ala135Val Uncertain significance ★ ⚠ same type
EID2 p.Ala187Thr Uncertain significance ★ ⚠ same type
EID2 p.Ala194Gly Uncertain significance ★ ⚠ same type
EID2 p.Ala49Val Uncertain significance ★ ⚠ same type
EID2 p.Ala50Thr Uncertain significance ★ ⚠ same type
EID2 p.Ala77Val Uncertain significance ★ ⚠ same type
EID2 p.Arg110Pro Uncertain significance ★ ⚠ same type
EID2 p.Arg128Gly 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/eid2-p-met63ile (accessed [today's date]).

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