EZH2 p.Thr421=
c.1263A>G · rs764997925 · VCV1613210
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Conditions
1
Weaver syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP -3.4 |
| Overall | ||
| CADD | 5.884 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/90,838 alleles
Overall
6.2e-05%
1/1,613,082 alleles · very rare
exomes 1/1,460,866 · genomes 0/152,216 · joint denominator
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.Thr421=
- Coding
- c.1263A>G
- MANE Select
- NM_004456
- dbSNP
- rs764997925
- Type
- single nucleotide variant
- Location
- chr7:148817369 (GRCh38)
- Gene constraint
- LOEUF 0.272 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.58 · 41 PDB
- Residue 421
- the 'interaction with cdyl' region; the 'disordered' region
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-thr421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown