Is EZH1 p.Ser429Pro (c.1285T>C) pathogenic?

EZH1 p.Ser429Pro (c.1285T>C) is classified Uncertain significance in EZH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-28). AlphaMissense: likely benign (0.0725); Absent from gnomAD v4.1.

How common is EZH1 p.Ser429Pro (c.1285T>C) in the general population?

EZH1 p.Ser429Pro (c.1285T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EZH1 p.Ser429Pro (c.1285T>C)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

EZH1 p.Ser429Pro

c.1285T>C · rs2543851885 · VCV2339995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
REVEL	0.493	indeterminate
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.6	GERP 0.5, phastCons 0.45
Regional constraint	o/e 0.58	unconstrained · MANE · 4,429 bp · p 7.1e-07 · regional, not allelic
Overall
CADD	13.56	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: EZH1
Protein: p.Ser429Pro
Coding: c.1285T>C
MANE Select: NM_001991
dbSNP: rs2543851885
Type: single nucleotide variant
Location: chr17:42712405 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.05 · 4 PDB

Full EZH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EZH1 p.Ala678Gly Pathogenic/Likely pathogenic ★★ same type
EZH1 p.Glu485Ter Likely pathogenic ★★ same type
EZH1 p.Ala268Gly Uncertain significance ★★ ⚠ same type
EZH1 p.Asp203Asn Uncertain significance ★★ ⚠ same type
EZH1 p.Leu735Phe Uncertain significance ★★ ⚠ same type
EZH1 c.1660+1G>A Likely pathogenic ★ same type
EZH1 c.932-1G>A Likely pathogenic ★ same type
EZH1 p.Gln731Glu Likely pathogenic ★ 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/ezh1-p-ser429pro (accessed [today's date]).

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