Is EP300 p.Pro1911del (c.5729CTC[1]) pathogenic?

EP300 p.Pro1911del (c.5729CTC[1]) is classified Benign in EP300 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-08-05). Ultra-rare (popmax 0.0267%, afr); Associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency.

What condition is associated with EP300 p.Pro1911del (c.5729CTC[1])?

EP300 p.Pro1911del (c.5729CTC[1]) is associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (ClinVar).

How common is EP300 p.Pro1911del (c.5729CTC[1]) in the general population?

EP300 p.Pro1911del (c.5729CTC[1]) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

EP300 p.Pro1911del

c.5729CTC[1] · rs755668623 · VCV2699782

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.6	GERP -4.8
Overall
CADD	16.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% African / African-American · 20/74,930 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00192% 31/1,614,092 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,746
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000763%	131,118

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.Pro1911del
Coding: c.5729CTC[1]
MANE Select: NM_001429
dbSNP: rs755668623
Type: Microsatellite
Location: chr22:41177439 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 1911: 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 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
EP300 p.Leu36fs 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-pro1911del (accessed [today's date]).

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