EP300 p.Ala1853=
c.5559C>A · rs141691930 · VCV2190039
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0308%, nfe)
Conditions
1
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
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 -0.82 | GERP -0.95, phastCons 0.001 |
| Overall | ||
| CADD | 6.386 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0308%
European (non-Finnish) · 363/1,180,032 alleles
Filtering AF
0.0281%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0271%
Overall
0.0228%
368/1,614,010 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0308% | 3,251 |
| African / African-American | 0.00401% | 24,963 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,245 |
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
- EP300
- Protein
- p.Ala1853=
- Coding
- c.5559C>A
- MANE Select
- NM_001429
- dbSNP
- rs141691930
- Type
- single nucleotide variant
- Location
- chr22:41177270 (GRCh38)
- Gene constraint
- LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.88 · 60 PDB
- Residue 1853
- the 'disordered' region
Similar variants
- EP300 p.Ala1853Gly Uncertain significance ★★ ⚠ same residue
- EP300 p.Ala1853_Pro1855del Uncertain significance ★★ same residue
- EP300 c.1282+1G>A Pathogenic/Likely pathogenic ★★ same condition
- EP300 c.3671+1G>A Pathogenic/Likely pathogenic ★★ same condition
- EP300 c.3729-2A>G Pathogenic/Likely pathogenic ★★ same condition
- EP300 c.3857A>G Pathogenic/Likely pathogenic ★★ ⚠ same condition
- EP300 p.Arg1055Ter Pathogenic ★★ same condition
- EP300 p.Arg1312Ter 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/ep300-p-ala1853 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown