EP300 p.Pro2064=
c.6192C>A · rs370889984 · VCV2856372
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0841%, afr)
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 0.14 | GERP -2.3, phastCons 0.008 |
| Overall | ||
| CADD | 8.068 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0841%
African / African-American · 63/74,928 alleles
Filtering AF
0.0674%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0614%
Overall
0.00415%
67/1,614,082 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0841% | 1,189 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| Admixed American | 0.00167% | 60,004 |
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.Pro2064=
- Coding
- c.6192C>A
- MANE Select
- NM_001429
- dbSNP
- rs370889984
- Type
- single nucleotide variant
- Location
- chr22:41177903 (GRCh38)
- Gene constraint
- LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.88 · 60 PDB
- Residue 2064
- the 'interaction with htlv-1 tax' region; the 'interaction with ncoa2' region
Similar variants
- 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
- EP300 p.Arg1462Ter 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-pro2064 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown