EP300 p.Arg580Ter
c.1738C>T · rs137853038 · VCV6880
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 3 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 8 of 31 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 2.3, phastCons 1 |
| Overall | ||
| CADD | 40.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- EP300
- Protein
- p.Arg580Ter
- Coding
- c.1738C>T
- MANE Select
- NM_001429
- dbSNP
- rs137853038
- Type
- single nucleotide variant
- Location
- chr22:41137768 (GRCh38)
- Gene constraint
- LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.88 · 60 PDB
- Residue 580
- an α-helix; the kix domain; a modified residue (asymmetric dimethylarginine; by carm1)
Similar variants
- EP300 p.Arg580Gln Conflicting classifications of pathogenicity ★ same residue
- EP300 p.Arg580Gly 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-arg580ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown