Is EP300 p.Pro934Leu (c.2801C>T) pathogenic?

EP300 p.Pro934Leu (c.2801C>T) is classified Benign/Likely benign in EP300 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0903); Ultra-rare (popmax 0.0168%, amr); Associated with Inborn genetic diseases.

What condition is associated with EP300 p.Pro934Leu (c.2801C>T)?

EP300 p.Pro934Leu (c.2801C>T) is associated with Inborn genetic diseases, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (ClinVar).

How common is EP300 p.Pro934Leu (c.2801C>T) in the general population?

EP300 p.Pro934Leu (c.2801C>T) is ultra-rare (popmax 0.0168%, amr) (gnomAD).

What do computational predictors say about EP300 p.Pro934Leu (c.2801C>T)?

AlphaMissense predicts likely benign (score 0.0903) — an in-silico prediction, not a clinical call.

EP300 p.Pro934Leu

c.2801C>T · rs564126491 · VCV2153089

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0903 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0903	likely benign
REVEL	0.251	benign-leaning
SaProt	LLR -8.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 2.5, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 11 kb · p 0.024 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% Admixed American · 10/59,600 alleles

Filtering AF 0.00905% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00685%

Overall 0.00124% 20/1,608,098 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0168%	5,960
East Asian	0.00223%	44,788
African / African-American	0.00133%	75,000
South Asian	0.0011%	90,860
European (non-Finnish)	0.000594%	168,439

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.Pro934Leu
Coding: c.2801C>T
MANE Select: NM_001429
dbSNP: rs564126491
Type: single nucleotide variant
Location: chr22:41150182 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 934: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Similar variants

EP300 p.Pro934= Likely benign ★ 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
EP300 p.Arg1356Ter 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-pro934leu (accessed [today's date]).

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