EZH2 p.Ser271=
c.813T>C · rs1353630360 · VCV2824969
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00342%, nfe)
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 0.2 | GERP 0.48, phastCons 0.29 |
| Overall | ||
| CADD | 8.387 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00342%
European (non-Finnish) · 40/1,170,998 alleles
Filtering AF
0.00257%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00227%
Overall
0.00256%
41/1,599,430 alleles · very rare
exomes 39/1,447,190 · genomes 2/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00342% | 29,275 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,662 |
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.Ser271=
- Coding
- c.813T>C
- MANE Select
- NM_004456
- dbSNP
- rs1353630360
- Type
- single nucleotide variant
- Location
- chr7:148826548 (GRCh38)
- Gene constraint
- LOEUF 0.272 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.58 · 41 PDB
- Residue 271
- the 'interaction with dnmt1, dnmt3a and dnmt3b' region
Similar variants
- EZH2 p.Ser271Pro Uncertain significance ★ ⚠ same residue
- EZH2 p.Ser271Phe Uncertain significance ★ ⚠ same residue
- EZH2 p.Arg684Cys Pathogenic ★★ same condition
- EZH2 p.Glu745Lys Pathogenic/Likely pathogenic ★★ same condition
- EZH2 p.Ser695Leu 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
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-ser271 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown