Is EED p.Arg302Gly (c.904A>G) pathogenic?

EED p.Arg302Gly (c.904A>G) is classified Pathogenic in EED (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-07-11). AlphaMissense: likely pathogenic (0.9991); Very rare (popmax 8.5e-05%, nfe); Associated with Cohen-Gibson syndrome.

What condition is associated with EED p.Arg302Gly (c.904A>G)?

EED p.Arg302Gly (c.904A>G) is associated with Cohen-Gibson syndrome (ClinVar).

How common is EED p.Arg302Gly (c.904A>G) in the general population?

EED p.Arg302Gly (c.904A>G) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about EED p.Arg302Gly (c.904A>G)?

AlphaMissense predicts likely pathogenic (score 0.9991) — an in-silico prediction, not a clinical call.

EED p.Arg302Gly

c.904A>G · rs1131692175 · VCV430645

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9991 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cohen-Gibson syndrome

Computational evidence

Protein change
AlphaMissense	0.9991	likely pathogenic ✓ concordant with ClinVar · top 8% in EED
REVEL	0.506	indeterminate
SaProt	LLR -12.28	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.27	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 28 kb · p 8.5e-32 · regional, not allelic
Overall
CADD	27.0	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 8.5e-05% European (non-Finnish) · 1/1,177,050 alleles

Overall 6.87e-05% 1/1,456,436 alleles · very rare

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: EED
Protein: p.Arg302Gly
Coding: c.904A>G
MANE Select: NM_003797
dbSNP: rs1131692175
Type: single nucleotide variant
Location: chr11:86268499 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 302: the 'interaction with ezh2' region; the 'required for interaction with the matrix protein ma of hiv-1' region; a UniProt-annotated variant site (in cogis); a UniProt-annotated variant site (in cogis; decreased trimethylation of 'lys-27' of histone h3); a β-strand

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

Disease context

Cohen-Gibson syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EED p.Arg302Ser Likely pathogenic ★ same residue
EED p.Asn194Ser Pathogenic/Likely pathogenic ★★ same condition
EED p.Asp237Gly Likely pathogenic ★★ same condition
EED p.Ala17Val Uncertain significance ★★ ⚠ same condition
EED p.Arg4Met Uncertain significance ★★ ⚠ same condition
EED p.Lys83Ile Uncertain significance ★★ ⚠ same condition
EED c.267+20C>G Benign/Likely benign ★★ same condition
EED c.361-19G>A Likely benign ★★ same condition

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/eed-p-arg302gly (accessed [today's date]).

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