Is EED p.Ala378Val (c.1133C>T) pathogenic?

EED p.Ala378Val (c.1133C>T) is classified Likely pathogenic in EED (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). AlphaMissense: likely pathogenic (0.9115); No allele count reported in gnomAD v4.1 (AN 1,544,598); Associated with Cohen-Gibson syndrome.

What condition is associated with EED p.Ala378Val (c.1133C>T)?

EED p.Ala378Val (c.1133C>T) is associated with Cohen-Gibson syndrome (ClinVar).

How common is EED p.Ala378Val (c.1133C>T) in the general population?

EED p.Ala378Val (c.1133C>T) is no allele count reported in gnomAD v4.1 (AN 1,544,598) (gnomAD).

What do computational predictors say about EED p.Ala378Val (c.1133C>T)?

AlphaMissense predicts likely pathogenic (score 0.9115) — an in-silico prediction, not a clinical call.

EED p.Ala378Val

c.1133C>T · rs1593776227 · VCV802712

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9115 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,544,598)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cohen-Gibson syndrome

Computational evidence

Protein change
AlphaMissense	0.9115	likely pathogenic ✓ concordant with ClinVar
REVEL	0.396	indeterminate
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 28 kb · p 8.5e-32 · regional, not allelic
Overall
CADD	27.8	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

No allele count reported in gnomAD v4.1 (AN 1,544,598). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EED
Protein: p.Ala378Val
Coding: c.1133C>T
MANE Select: NM_003797
dbSNP: rs1593776227
Type: single nucleotide variant
Location: chr11:86277925 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 378: 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-ala378val (accessed [today's date]).

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