EP300 p.Val2273fs
c.6816del · VCV4823914
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
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. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (31 of 31) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.8, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- EP300
- Protein
- p.Val2273fs
- Coding
- c.6816del
- MANE Select
- NM_001429
- Type
- Deletion
- Location
- chr22:41178527 (GRCh38)
- Gene constraint
- LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.88 · 60 PDB
- Residue 2273
- the 'disordered' region
Similar variants
- EP300 p.Asn2305fs Pathogenic/Likely pathogenic ★★ same condition
- EP300 p.Ile1457_Lys1459delinsMet Pathogenic/Likely pathogenic ★★ same condition
- EP300 p.Ile2100fs Pathogenic/Likely pathogenic ★★ same condition
- EP300 p.Lys1228fs Pathogenic ★★ same condition
- EP300 p.Pro742fs Pathogenic ★★ same condition
- EP300 p.Ser457fs Pathogenic ★★ same condition
- EP300 p.Ala1853_Pro1855del Uncertain significance ★★ same condition
- EP300 p.Arg1645_Ala1647delinsPro 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/ep300-p-val2273fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown