EZH2 p.Ser695=
c.2085G>A · VCV4742979
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00224%, eas)
Conditions
1
Weaver syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.7 | GERP -3.5 |
| Overall | ||
| CADD | 8.974 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00224%
East Asian · 1/44,558 alleles
Filtering AF
0.000184%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000121%
Overall
0.000499%
8/1,603,486 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00224% | 44,558 |
| South Asian | 0.0011% | 90,758 |
| European (non-Finnish) | 0.000512% | 195,189 |
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.Ser695=
- Coding
- c.2085G>A
- MANE Select
- NM_004456
- Type
- single nucleotide variant
- Location
- chr7:148809335 (GRCh38)
- Gene constraint
- LOEUF 0.272 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.58 · 41 PDB
- Residue 695
- a β-strand; the set domain
Similar variants
- EZH2 p.Ser695Leu Pathogenic/Likely pathogenic ★★ same residue
- EZH2 p.Arg684Cys Pathogenic ★★ same condition
- EZH2 p.Glu745Lys Pathogenic/Likely pathogenic ★★ same condition
- EZH2 p.Tyr133Cys Pathogenic/Likely pathogenic ★★ same condition
- EZH2 p.Val626Met Pathogenic ★★ same condition
- EZH2 p.Val679Leu Likely pathogenic ★★ same condition
- EZH2 c.626-3T>C Uncertain significance ★★ same condition
- EZH2 p.Ala255Val 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-ser695 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown