EZH2 p.Asp124=
c.372T>C · rs765380980 · VCV702117
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, 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 5.4 | GERP 0.54, phastCons 1 |
| Overall | ||
| CADD | 7.608 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
European (non-Finnish) · 139/1,155,596 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00976%
Overall
0.00911%
143/1,570,048 alleles · ultra-rare
exomes 138/1,417,850 · genomes 5/152,198 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.012% | 8,314 |
| Remaining individualsnot grpmax-eligible | 0.00492% | 20,316 |
| African / African-American | 0.00137% | 72,910 |
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.Asp124=
- Coding
- c.372T>C
- MANE Select
- NM_004456
- dbSNP
- rs765380980
- Type
- single nucleotide variant
- Location
- chr7:148829840 (GRCh38)
- Gene constraint
- LOEUF 0.272 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.58 · 41 PDB
- Residue 124
- the 'interaction with dnmt1, dnmt3a and dnmt3b' region; an α-helix
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-asp124 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown