Is EED p.Leu207= (c.619C>T) pathogenic?

EED p.Leu207= (c.619C>T) is classified Benign in EED (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 41%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Cohen-Gibson syndrome.

What condition is associated with EED p.Leu207= (c.619C>T)?

EED p.Leu207= (c.619C>T) is associated with Cohen-Gibson syndrome (ClinVar).

EED p.Leu207=

Q: How common is EED p.Leu207= (c.619C>T) in the general population?

EED p.Leu207= (c.619C>T) is common (popmax 41%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.619C>T · rs974144 · VCV1165047

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 41%, nfe) — too common for a highly-penetrant pathogenic allele

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 0.63	GERP -1.2, phastCons 0.12
Overall
CADD	7.433	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 41% European (non-Finnish) · 482,551/1,175,770 alleles

Filtering AF 40.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 40.9%

Overall 38.9% 625,755/1,607,006 alleles · common exomes 575,215/1,455,054 · genomes 50,540/151,952 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	51.4%	2
Finnishnot grpmax-eligible	42.8%	2
European (non-Finnish)grpmax	41%	2
South Asian	39.2%	3
Remaining individualsnot grpmax-eligible	37.2%	3
East Asian	36.7%	3
Middle Eastern	35.5%	3
Ashkenazi Jewishnot grpmax-eligible	30.9%	3
Admixed American	27.8%	4
African / African-American	17.2%	6

Amish 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.Leu207=
Coding: c.619C>T
MANE Select: NM_003797
dbSNP: rs974144
Type: single nucleotide variant
Location: chr11:86257581 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 207: the 'interaction with ezh2' region; the 'required for interaction with the matrix protein ma of hiv-1' 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 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-leu207 (accessed [today's date]).

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