Is EOMES p.Val317Ile (c.949G>A) pathogenic?

EOMES p.Val317Ile (c.949G>A) is classified Uncertain significance in EOMES (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: ambiguous (0.4957); Very rare (popmax 0.00167%, amr).

How common is EOMES p.Val317Ile (c.949G>A) in the general population?

EOMES p.Val317Ile (c.949G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about EOMES p.Val317Ile (c.949G>A)?

AlphaMissense predicts ambiguous (score 0.4957) — an in-silico prediction, not a clinical call.

EOMES p.Val317Ile

c.949G>A · VCV3508817

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4957 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.4957	ambiguous
REVEL	0.416	indeterminate
SaProt	LLR -6.57	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 3,755 bp · p 5.6e-09 · regional, not allelic
Overall
CADD	31.0	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 0.00167% Admixed American · 1/59,976 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000434% 7/1,613,624 alleles · very rare exomes 5/1,461,502 · genomes 2/152,122 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,616
Admixed Americangrpmax	0.00167%	59,976
European (non-Finnish)	0.00017%	589,890

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val317Ile
Coding: c.949G>A
MANE Select: NM_001278182
Type: single nucleotide variant
Location: chr3:27720258 (GRCh38)
Gene constraint: LOEUF 0.493 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 56.74
Residue 317: a DNA-binding 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-val317ile (accessed [today's date]).

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