EP300 p.Ser1396=
c.4188T>A · rs765022504 · VCV2100598
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 -0.01 | GERP -1.9, phastCons 0.53 |
| Overall | ||
| CADD | 8.245 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,994 alleles
Filtering AF
0.000881%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00072%
Overall
0.00112%
18/1,606,886 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,994 |
| European (non-Finnish) | 0.00145% | 69,159 |
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.Ser1396=
- Coding
- c.4188T>A
- MANE Select
- NM_001429
- dbSNP
- rs765022504
- Type
- single nucleotide variant
- Location
- chr22:41169518 (GRCh38)
- Gene constraint
- LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.88 · 60 PDB
- Residue 1396
- a β-strand; the cbp/p300-type hat domain
Similar variants
- EP300 p.Ser1396Pro Conflicting classifications of pathogenicity ★ ⚠ 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
- EP300 p.Arg1356Ter 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-ser1396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown