Is EED p.Lys72= (c.216A>G) pathogenic?

EED p.Lys72= (c.216A>G) is classified Likely benign in EED (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-04). Ultra-rare (popmax 0.0255%, afr); Associated with Cohen-Gibson syndrome.

What condition is associated with EED p.Lys72= (c.216A>G)?

EED p.Lys72= (c.216A>G) is associated with Cohen-Gibson syndrome (ClinVar).

How common is EED p.Lys72= (c.216A>G) in the general population?

EED p.Lys72= (c.216A>G) is ultra-rare (popmax 0.0255%, afr) (gnomAD).

EED p.Lys72=

c.216A>G · rs369391559 · VCV2141107

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0255%, afr)

Conditions

Cohen-Gibson syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.1, phastCons 1
Overall
CADD	10.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0255% African / African-American · 19/74,474 alleles

Filtering AF 0.0167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00211% 34/1,608,658 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0255%	3,920
Remaining individualsnot grpmax-eligible	0.0209%	4,791
European (non-Finnish)	0.00017%	588,900

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.Lys72=
Coding: c.216A>G
MANE Select: NM_003797
dbSNP: rs369391559
Type: single nucleotide variant
Location: chr11:86250397 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 72: the 'disordered' region

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.Lys72Arg Uncertain significance ★ ⚠ 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-lys72 (accessed [today's date]).

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