EZH2 p.Phe339=
c.1017T>C · rs77051363 · VCV158576
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.23%, afr)
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 -2.1 | GERP -3.4 |
| Overall | ||
| CADD | 1.021 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.23%
African / African-American · 3,125/73,958 alleles
Filtering AF
4.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.05%
Overall
0.224%
3,571/1,594,402 alleles · low-frequency
exomes 1,688/1,442,080 · genomes 1,883/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.23% | 24 |
| Remaining individualsnot grpmax-eligible | 0.343% | 292 |
| Admixed American | 0.294% | 340 |
| Middle Eastern | 0.258% | 388 |
| South Asian | 0.0114% | 8,779 |
| European (non-Finnish) | 0.00376% | 26,617 |
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.Phe339=
- Coding
- c.1017T>C
- MANE Select
- NM_004456
- dbSNP
- rs77051363
- Type
- single nucleotide variant
- Location
- chr7:148818100 (GRCh38)
- Gene constraint
- LOEUF 0.272 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.58 · 41 PDB
Similar variants
- 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
- 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-phe339 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown