Is EP300 p.Tyr751fs (c.2251_2257del) pathogenic?

EP300 p.Tyr751fs (c.22512257del) is classified Pathogenic in EP300 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-03-29). Absent from gnomAD; Associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency.

What condition is associated with EP300 p.Tyr751fs (c.2251_2257del)?

EP300 p.Tyr751fs (c.2251_2257del) is associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (ClinVar).

How common is EP300 p.Tyr751fs (c.2251_2257del) in the general population?

EP300 p.Tyr751fs (c.2251_2257del) is absent from gnomAD (gnomAD).

EP300 p.Tyr751fs

c.2251_2257del · rs1601618876 · VCV827623

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

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	predicted	premature termination codon in exon 13 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 2.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EP300
Protein: p.Tyr751fs
Coding: c.2251_2257del
MANE Select: NM_001429
dbSNP: rs1601618876
Type: Microsatellite
Location: chr22:41149039 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 751: the 'disordered' region

Full EP300 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EP300 p.Ser35fs Pathogenic/Likely pathogenic ★★ same condition
EP300 c.1760+6_1760+9del Uncertain significance ★★ same condition
EP300 p.Thr858_Ile859insThr Uncertain significance ★★ same condition
EP300 p.Tyr751Cys Uncertain significance ★★ ⚠ same residue
EP300 c.4780-11_4780-8del Likely benign ★★ same condition
EP300 p.Ala394fs Pathogenic ★ same condition
EP300 p.Cys1790del Likely pathogenic ★ same condition
EP300 p.Gln2408fs 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-tyr751fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown