Is EOMES p.Ile682Val (c.2044A>G) pathogenic?

EOMES p.Ile682Val (c.2044A>G) is classified Uncertain significance in EOMES (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely benign (0.0684); Very rare (popmax 6.2e-05%).

How common is EOMES p.Ile682Val (c.2044A>G) in the general population?

EOMES p.Ile682Val (c.2044A>G) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about EOMES p.Ile682Val (c.2044A>G)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

EOMES p.Ile682Val

c.2044A>G · VCV4664548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -6.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.98	GERP 1.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 685 bp · p 0.17 · regional, not allelic
Overall
CADD	16.82	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I663V vs ClinVar I682V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,612,480 alleles · very rare exomes 1/1,460,138 · genomes 0/152,342 · joint denominator

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: EOMES
Protein: p.Ile682Val
Coding: c.2044A>G
MANE Select: NM_001278182
Type: single nucleotide variant
Location: chr3:27717144 (GRCh38)
Gene constraint: LOEUF 0.493 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 56.74
Residue 663 UniProt numbering: the 'required for transcription activation' region; the 'disordered' region

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

Similar variants

EOMES p.Tyr231Cys Uncertain significance ★★ ⚠ same type
EOMES p.Glu113= Likely benign ★★ same type
EOMES p.Pro641= Benign ★★ same type
EOMES p.Ser392= Likely benign ★★ same type
EOMES p.Ser91Arg Likely benign ★★ same type
EOMES p.Ala118Pro Uncertain significance ★ ⚠ same type
EOMES p.Ala17Pro Uncertain significance ★ ⚠ same type
EOMES p.Ala206Gly 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/eomes-p-ile682val (accessed [today's date]).

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