EZH2 p.Thr573=
c.1719C>A · rs186989444 · VCV459201
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.193%, amr)
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 1.4 | GERP 0.81, phastCons 1 |
| Overall | ||
| CADD | 7.957 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.193%
Admixed American · 116/60,010 alleles
Filtering AF
0.165%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.154%
Overall
0.00762%
123/1,614,098 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.193% | 517 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,929 |
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.Thr573=
- Coding
- c.1719C>A
- MANE Select
- NM_004456
- dbSNP
- rs186989444
- Type
- single nucleotide variant
- Location
- chr7:148814091 (GRCh38)
- Gene constraint
- LOEUF 0.272 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.58 · 41 PDB
- Residue 573
- the cxc domain; an α-helix
Similar variants
- EZH2 p.Thr573Ser 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
- EZH2 c.626-3T>C 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-thr573 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown