Is EED p.Lys66= (c.198A>G) pathogenic?

EED p.Lys66= (c.198A>G) is classified Likely benign in EED (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-01). Ultra-rare (popmax 0.0165%, mid); Associated with Cohen-Gibson syndrome.

What condition is associated with EED p.Lys66= (c.198A>G)?

EED p.Lys66= (c.198A>G) is associated with Cohen-Gibson syndrome (ClinVar).

How common is EED p.Lys66= (c.198A>G) in the general population?

EED p.Lys66= (c.198A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

EED p.Lys66=

c.198A>G · rs182106684 · VCV544590

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 2.1	GERP -0.071, phastCons 1
Overall
CADD	7.974	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,048 alleles

Filtering AF 0.00439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00362%

Overall 0.00454% 73/1,608,864 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,048
African / African-American	0.00939%	10,655
Remaining individualsnot grpmax-eligible	0.00642%	15,579
European (non-Finnish)	0.00509%	19,630
South Asian	0.00111%	90,346

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.Lys66=
Coding: c.198A>G
MANE Select: NM_003797
dbSNP: rs182106684
Type: single nucleotide variant
Location: chr11:86250379 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 66: a modified residue (n6,n6,n6-trimethyllysine; alternate); a modified residue (n6,n6-dimethyllysine; alternate); a modified residue (n6-methyllysine; alternate); 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.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-lys66 (accessed [today's date]).

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