Is EED p.Ile274Val (c.820A>G) pathogenic?

EED p.Ile274Val (c.820A>G) is classified Likely benign in EED (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-01). AlphaMissense: likely benign (0.0859); Ultra-rare (popmax 0.0235%, amr); Associated with Cohen-Gibson syndrome.

What condition is associated with EED p.Ile274Val (c.820A>G)?

EED p.Ile274Val (c.820A>G) is associated with Cohen-Gibson syndrome (ClinVar).

How common is EED p.Ile274Val (c.820A>G) in the general population?

EED p.Ile274Val (c.820A>G) is ultra-rare (popmax 0.0235%, amr) (gnomAD).

What do computational predictors say about EED p.Ile274Val (c.820A>G)?

AlphaMissense predicts likely benign (score 0.0859) — an in-silico prediction, not a clinical call.

EED p.Ile274Val

c.820A>G · rs367891435 · VCV800180

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0859 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0235%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cohen-Gibson syndrome

Computational evidence

Protein change
AlphaMissense	0.0859	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -8.38	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 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 28 kb · p 8.5e-32 · regional, not allelic
Overall
CADD	21.8	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 0.0235% Admixed American · 14/59,532 alleles

Filtering AF 0.0142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0113%

Overall 0.0112% 179/1,604,584 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.408%	245
Remaining individualsnot grpmax-eligible	0.0241%	4,141
Admixed Americangrpmax	0.0235%	4,252
African / African-American	0.00802%	12,471
South Asian	0.00333%	30,033
European (non-Finnish)	0.00179%	55,869

Ashkenazi Jewish 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: EED
Protein: p.Ile274Val
Coding: c.820A>G
MANE Select: NM_003797
dbSNP: rs367891435
Type: single nucleotide variant
Location: chr11:86266176 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 274: the 'interaction with ezh2' region; the 'required for interaction with the matrix protein ma of hiv-1' region; an α-helix

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.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
EED c.727-8G>A 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-ile274val (accessed [today's date]).

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