Is EZH2 p.Asp187Glu (c.561T>A) pathogenic?

EZH2 p.Asp187Glu (c.561T>A) is classified Uncertain significance in EZH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). AlphaMissense: likely benign (0.0896); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EZH2 p.Asp187Glu (c.561T>A)?

EZH2 p.Asp187Glu (c.561T>A) is associated with Inborn genetic diseases (ClinVar).

How common is EZH2 p.Asp187Glu (c.561T>A) in the general population?

EZH2 p.Asp187Glu (c.561T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EZH2 p.Asp187Glu (c.561T>A)?

AlphaMissense predicts likely benign (score 0.0896) — an in-silico prediction, not a clinical call.

EZH2 p.Asp187Glu

c.561T>A · VCV3511190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0896 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0896	likely benign
REVEL	0.342	indeterminate
SaProt	LLR -7.20	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -3.4
Regional constraint	o/e 0.88	unconstrained · MANE · 1,658 bp · p 0.29 · regional, not allelic
Overall
CADD	0.385	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EZH2
Protein: p.Asp187Glu
Coding: c.561T>A
MANE Select: NM_004456
Type: single nucleotide variant
Location: chr7:148828804 (GRCh38)
Gene constraint: LOEUF 0.272 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.58 · 41 PDB
Residue 187: the 'interaction with dnmt1, dnmt3a and dnmt3b' region; the 'disordered' region

Full EZH2 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

EZH2 p.Asp187_Asp189del Uncertain significance ★ same residue
EZH2 p.Asp187Asn Benign ★ same residue
EZH2 p.Ala255Val Uncertain significance ★★ ⚠ same condition
EZH2 p.Arg34Gln Uncertain significance ★★ ⚠ same condition
EZH2 p.Arg712Lys Uncertain significance ★★ ⚠ same condition
EZH2 p.Asn416Asp Uncertain significance ★★ ⚠ same condition
EZH2 p.Gly394Ala Uncertain significance ★★ ⚠ same condition
EZH2 p.Asp136His Likely pathogenic ★ 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/ezh2-p-asp187glu (accessed [today's date]).

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