Is EED p.Glu392Lys (c.1174G>A) pathogenic?

EED p.Glu392Lys (c.1174G>A) is classified Uncertain significance in EED (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-07). AlphaMissense: likely pathogenic (0.8271); Very rare (popmax 0.00243%, eas); Associated with Inborn genetic diseases.

What condition is associated with EED p.Glu392Lys (c.1174G>A)?

EED p.Glu392Lys (c.1174G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EED p.Glu392Lys (c.1174G>A) in the general population?

EED p.Glu392Lys (c.1174G>A) is very rare (popmax 0.00243%, eas) (gnomAD).

What do computational predictors say about EED p.Glu392Lys (c.1174G>A)?

AlphaMissense predicts likely pathogenic (score 0.8271) — an in-silico prediction, not a clinical call.

EED p.Glu392Lys

c.1174G>A · rs762517406 · VCV2558595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8271 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00243%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8271	likely pathogenic
REVEL	0.348	indeterminate
SaProt	LLR -7.42	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 28 kb · p 8.5e-32 · regional, not allelic
Overall
CADD	25.8	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 0.00243% East Asian · 1/41,216 alleles

Overall 7.2e-05% 1/1,388,204 alleles · very rare

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.Glu392Lys
Coding: c.1174G>A
MANE Select: NM_003797
dbSNP: rs762517406
Type: single nucleotide variant
Location: chr11:86277966 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 392: the 'interaction with ezh2' region; the 'required for interaction with the matrix protein ma of hiv-1' region

Full EED gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EED c.268-3T>C Conflicting classifications of pathogenicity ★ same condition
EED p.Ala327Ser Uncertain significance ★ ⚠ same condition
EED p.Ala41Thr Uncertain significance ★ ⚠ same condition
EED p.Arg4Ser Uncertain significance ★ ⚠ same condition
EED p.Asn102Asp Uncertain significance ★ ⚠ same condition
EED p.Asn266Thr Uncertain significance ★ ⚠ same condition
EED p.Asn272Ser Uncertain significance ★ ⚠ same condition
EED p.Asn38Thr Uncertain significance ★ ⚠ 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-glu392lys (accessed [today's date]).

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