Is EED p.Lys83Ile (c.248A>T) pathogenic?

EED p.Lys83Ile (c.248A>T) is classified Uncertain significance in EED (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-28). AlphaMissense: likely pathogenic (0.8198); Absent from gnomAD v4.1; Associated with Cohen-Gibson syndrome.

What condition is associated with EED p.Lys83Ile (c.248A>T)?

EED p.Lys83Ile (c.248A>T) is associated with Cohen-Gibson syndrome (ClinVar).

How common is EED p.Lys83Ile (c.248A>T) in the general population?

EED p.Lys83Ile (c.248A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EED p.Lys83Ile (c.248A>T)?

AlphaMissense predicts likely pathogenic (score 0.8198) — an in-silico prediction, not a clinical call.

EED p.Lys83Ile

c.248A>T · VCV4527796

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8198 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cohen-Gibson syndrome

Computational evidence

Protein change
AlphaMissense	0.8198	likely pathogenic
REVEL	0.323	indeterminate
SaProt	LLR -10.28	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 28 kb · p 8.5e-32 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EED
Protein: p.Lys83Ile
Coding: c.248A>T
MANE Select: NM_003797
Type: single nucleotide variant
Location: chr11:86250429 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 83: the 'interaction with ezh2' region; 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.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 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
EED p.Asp26= 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-lys83ile (accessed [today's date]).

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