Is EZH2 p.Ser73Phe (c.218C>T) pathogenic?

EZH2 p.Ser73Phe (c.218C>T) is classified Uncertain significance in EZH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-25). AlphaMissense: likely benign (0.2318); Absent from gnomAD v4.1.

How common is EZH2 p.Ser73Phe (c.218C>T) in the general population?

EZH2 p.Ser73Phe (c.218C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EZH2 p.Ser73Phe (c.218C>T)?

AlphaMissense predicts likely benign (score 0.2318) — an in-silico prediction, not a clinical call.

EZH2 p.Ser73Phe

c.218C>T · rs2129484932 · VCV1329716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2318 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2318	likely benign
REVEL	0.561	indeterminate
SaProt	LLR -10.46	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 15 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	32.0	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

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.Ser73Phe
Coding: c.218C>T
MANE Select: NM_004456
dbSNP: rs2129484932
Type: single nucleotide variant
Location: chr7:148846498 (GRCh38)
Gene constraint: LOEUF 0.272 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.58 · 41 PDB
Residue 73: the 'interaction with dnmt1, dnmt3a and dnmt3b' region

Full EZH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EZH2 p.Arg684Cys Pathogenic ★★ same type
EZH2 p.Glu745Lys Pathogenic/Likely pathogenic ★★ same type
EZH2 p.Ser695Leu Pathogenic/Likely pathogenic ★★ same type
EZH2 p.Tyr133Cys Pathogenic/Likely pathogenic ★★ same type
EZH2 p.Tyr741His Likely pathogenic ★★ same type
EZH2 p.Val626Met Pathogenic ★★ same type
EZH2 p.Val679Leu Likely pathogenic ★★ same type
EZH2 c.626-3T>C Uncertain significance ★★ 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/ezh2-p-ser73phe (accessed [today's date]).

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