EZH2 p.Phe145Cys
c.434T>G · VCV3393823
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9999 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9999 | likely pathogenic ✓ concordant with ClinVar · top 9% in EZH2 |
|---|---|---|
| REVEL | 0.909 | moderately pathogenic-leaning |
| SaProt | LLR -13.78 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.3 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.25 | constrained · MANE · 3,839 bp · p 5.6e-12 · regional, not allelic |
| Overall | ||
| CADD | 27.2 | 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.Phe145Cys
- Coding
- c.434T>G
- MANE Select
- NM_004456
- Type
- single nucleotide variant
- Location
- chr7:148829778 (GRCh38)
- Gene constraint
- LOEUF 0.272 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.58 · 41 PDB
- Residue 145
- the 'interaction with dnmt1, dnmt3a and dnmt3b' region; an α-helix
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-phe145cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown