Is EED p.Ile426Met (c.1278A>G) pathogenic?

EED p.Ile426Met (c.1278A>G) is classified Uncertain significance in EED (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-24). AlphaMissense: ambiguous (0.4307); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EED p.Ile426Met (c.1278A>G)?

EED p.Ile426Met (c.1278A>G) is associated with Inborn genetic diseases (ClinVar).

How common is EED p.Ile426Met (c.1278A>G) in the general population?

EED p.Ile426Met (c.1278A>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about EED p.Ile426Met (c.1278A>G)?

AlphaMissense predicts ambiguous (score 0.4307) — an in-silico prediction, not a clinical call.

EED p.Ile426Met

c.1278A>G · rs951387529 · VCV2227905

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4307 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4307	ambiguous
REVEL	0.18	moderately benign-leaning
SaProt	LLR -9.25	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 28 kb · p 8.5e-32 · regional, not allelic
Overall
CADD	24.3	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 0.00017% European (non-Finnish) · 2/1,179,844 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00131% 2/152,230 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.Ile426Met
Coding: c.1278A>G
MANE Select: NM_003797
dbSNP: rs951387529
Type: single nucleotide variant
Location: chr11:86278477 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 426: the 'interaction with ezh2' region; a β-strand; 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 p.Ile426Val Uncertain significance ★ ⚠ same residue
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

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-ile426met (accessed [today's date]).

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