Is EOMES p.Pro641= (c.1923C>T) pathogenic?

EOMES p.Pro641= (c.1923C>T) is classified Benign in EOMES (ClinVar, Multiple submitters, 2 submitters; last evaluated 2014-01-28). Common (popmax 12.8%, afr) — too common for a highly-penetrant pathogenic allele.

EOMES p.Pro641=

Q: How common is EOMES p.Pro641= (c.1923C>T) in the general population?

EOMES p.Pro641= (c.1923C>T) is common (popmax 12.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1923C>T · rs6783101 · VCV137211

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 12.8%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.016	GERP -3.4, phastCons 0.063
Overall
CADD	5.982	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.8% African / African-American · 9,608/74,962 alleles

Filtering AF 12.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.5%

Overall 0.693% 11,188/1,613,452 alleles · common exomes 5,684/1,461,202 · genomes 5,504/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.8%	8
Remaining individualsnot grpmax-eligible	0.936%	107
Admixed American	0.928%	108
Middle Eastern	0.577%	173
South Asian	0.0329%	3,036
European (non-Finnish)	0.0316%	3,162

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.Pro641=
Coding: c.1923C>T
MANE Select: NM_001278182
dbSNP: rs6783101
Type: single nucleotide variant
Location: chr3:27717265 (GRCh38)
Gene constraint: LOEUF 0.493 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 56.74
Residue 641: 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.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
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-pro641 (accessed [today's date]).

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