Is EED p.Lys250Thr (c.749A>C) pathogenic?

EED p.Lys250Thr (c.749A>C) is classified Uncertain significance in EED (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-06). AlphaMissense: likely pathogenic (0.8151); Very rare (popmax 8.53e-05%, nfe).

How common is EED p.Lys250Thr (c.749A>C) in the general population?

EED p.Lys250Thr (c.749A>C) is very rare (popmax 8.53e-05%, nfe) (gnomAD).

What do computational predictors say about EED p.Lys250Thr (c.749A>C)?

AlphaMissense predicts likely pathogenic (score 0.8151) — an in-silico prediction, not a clinical call.

EED p.Lys250Thr

c.749A>C · rs2138196928 · VCV1303707

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8151 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.53e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8151	likely pathogenic
REVEL	0.56	indeterminate
SaProt	LLR -11.58	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
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	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.53e-05% European (non-Finnish) · 1/1,172,282 alleles

Overall 6.92e-05% 1/1,444,398 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.Lys250Thr
Coding: c.749A>C
MANE Select: NM_003797
dbSNP: rs2138196928
Type: single nucleotide variant
Location: chr11:86266105 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 250: 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

Similar variants

EED p.Asn194Ser Pathogenic/Likely pathogenic ★★ same type
EED p.Asp237Gly Likely pathogenic ★★ same type
EED p.Ala17Val Uncertain significance ★★ ⚠ same type
EED p.Arg4Met Uncertain significance ★★ ⚠ same type
EED p.Lys83Ile Uncertain significance ★★ ⚠ same type
EED c.267+20C>G Benign/Likely benign ★★ same type
EED c.268-43G>A Benign ★★ same type
EED c.361-19G>A Likely benign ★★ same type

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-lys250thr (accessed [today's date]).

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