Is EZH2 p.Arg34Gln (c.101G>A) pathogenic?

EZH2 p.Arg34Gln (c.101G>A) is classified Uncertain significance in EZH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-22). AlphaMissense: likely pathogenic (0.905); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EZH2 p.Arg34Gln (c.101G>A)?

EZH2 p.Arg34Gln (c.101G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EZH2 p.Arg34Gln (c.101G>A) in the general population?

EZH2 p.Arg34Gln (c.101G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about EZH2 p.Arg34Gln (c.101G>A)?

AlphaMissense predicts likely pathogenic (score 0.905) — an in-silico prediction, not a clinical call.

EZH2 p.Arg34Gln

c.101G>A · rs2129485367 · VCV1700793

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.905 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.905	likely pathogenic
REVEL	0.562	indeterminate
SaProt	LLR -4.69	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 6.6, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 15 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	29.0	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 8.48e-05% European (non-Finnish) · 1/1,179,290 alleles

Overall 6.21e-05% 1/1,611,376 alleles · very rare exomes 1/1,459,076 · genomes 0/152,300 · joint denominator

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: EZH2
Protein: p.Arg34Gln
Coding: c.101G>A
MANE Select: NM_004456
dbSNP: rs2129485367
Type: single nucleotide variant
Location: chr7:148847198 (GRCh38)
Gene constraint: LOEUF 0.272 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.58 · 41 PDB
Residue 34: the 'interaction with dnmt1, dnmt3a and dnmt3b' 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.Arg34= Likely benign ★ same residue
EZH2 p.Ala255Val 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
EZH2 p.Ala269Asp Uncertain significance ★ ⚠ same condition
EZH2 p.Ala269Val 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/ezh2-p-arg34gln (accessed [today's date]).

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