Is EOMES p.Ala118Pro (c.352G>C) pathogenic?

EOMES p.Ala118Pro (c.352G>C) is classified Uncertain significance in EOMES (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-05). AlphaMissense: likely benign (0.1121); Very rare (popmax 0.000463%, nfe).

How common is EOMES p.Ala118Pro (c.352G>C) in the general population?

EOMES p.Ala118Pro (c.352G>C) is very rare (popmax 0.000463%, nfe) (gnomAD).

What do computational predictors say about EOMES p.Ala118Pro (c.352G>C)?

AlphaMissense predicts likely benign (score 0.1121) — an in-silico prediction, not a clinical call.

EOMES p.Ala118Pro

c.352G>C · rs764028457 · VCV2609545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1121 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000463%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1121	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -10.36	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.1, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 779 bp · p 0.00084 · regional, not allelic
Overall
CADD	21.1	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 0.000463% European (non-Finnish) · 5/1,080,712 alleles

Filtering AF 0.000136% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.9e-05%

Overall 0.00036% 5/1,387,252 alleles · very rare exomes 5/1,235,328 · genomes 0/151,924 · 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.Ala118Pro
Coding: c.352G>C
MANE Select: NM_001278182
dbSNP: rs764028457
Type: single nucleotide variant
Location: chr3:27721943 (GRCh38)
Gene constraint: LOEUF 0.493 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 56.74

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.Ala17Pro Uncertain significance ★ ⚠ same type
EOMES p.Ala206Gly Uncertain significance ★ ⚠ same type
EOMES p.Ala218Thr 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-ala118pro (accessed [today's date]).

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