Is EOMES p.Pro100Ser (c.298C>T) pathogenic?

EOMES p.Pro100Ser (c.298C>T) is classified Uncertain significance in EOMES (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-27). AlphaMissense: likely benign (0.0615); Ultra-rare (popmax 0.0476%, sas).

How common is EOMES p.Pro100Ser (c.298C>T) in the general population?

EOMES p.Pro100Ser (c.298C>T) is ultra-rare (popmax 0.0476%, sas) (gnomAD).

What do computational predictors say about EOMES p.Pro100Ser (c.298C>T)?

AlphaMissense predicts likely benign (score 0.0615) — an in-silico prediction, not a clinical call.

EOMES p.Pro100Ser

c.298C>T · rs758047037 · VCV2257664

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0615 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0476%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0615	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -4.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 779 bp · p 0.00084 · regional, not allelic
Overall
CADD	23.1	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 0.0476% South Asian · 36/75,674 alleles

Filtering AF 0.0353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0311%

Overall 0.00284% 42/1,477,168 alleles · ultra-rare exomes 38/1,325,214 · genomes 4/151,954 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0476%	2,102
Middle Eastern	0.0216%	4,628
Remaining individualsnot grpmax-eligible	0.00528%	18,941
Ashkenazi Jewishnot grpmax-eligible	0.00381%	26,260
African / African-American	0.00149%	67,216

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.Pro100Ser
Coding: c.298C>T
MANE Select: NM_001278182
dbSNP: rs758047037
Type: single nucleotide variant
Location: chr3:27721997 (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.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-pro100ser (accessed [today's date]).

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