Is EED p.Ile178Val (c.532A>G) pathogenic?

EED p.Ile178Val (c.532A>G) is classified Conflicting classifications of pathogenicity in EED (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-11-11). AlphaMissense: likely benign (0.0709); Ultra-rare (popmax 0.0864%, nfe); Associated with Cohen-Gibson syndrome.

What condition is associated with EED p.Ile178Val (c.532A>G)?

EED p.Ile178Val (c.532A>G) is associated with Cohen-Gibson syndrome (ClinVar).

How common is EED p.Ile178Val (c.532A>G) in the general population?

EED p.Ile178Val (c.532A>G) is ultra-rare (popmax 0.0864%, nfe) (gnomAD).

What do computational predictors say about EED p.Ile178Val (c.532A>G)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

EED p.Ile178Val

c.532A>G · rs147440081 · VCV971694

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0864%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cohen-Gibson syndrome

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -0.76	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	20.8	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 0.0864% European (non-Finnish) · 1,018/1,177,696 alleles

Filtering AF 0.082% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0802%

Overall 0.0668% 1,075/1,610,186 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0864%	1,157
Remaining individualsnot grpmax-eligible	0.0466%	2,148
Middle Eastern	0.033%	3,034
African / African-American	0.0174%	5,757
Admixed American	0.0151%	6,628
Finnishnot grpmax-eligible	0.0047%	21,299
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,526

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.Ile178Val
Coding: c.532A>G
MANE Select: NM_003797
dbSNP: rs147440081
Type: single nucleotide variant
Location: chr11:86256492 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 178: the 'interaction with ezh2' region; the 'required for interaction with the matrix protein ma of hiv-1' region; a turn

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-ile178val (accessed [today's date]).

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