Is EP300 p.Pro882Arg (c.2645C>G) pathogenic?

EP300 p.Pro882Arg (c.2645C>G) is classified Benign/Likely benign in EP300 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-30). AlphaMissense: likely benign (0.1226); Ultra-rare (popmax 0.0493%, mid); Associated with Inborn genetic diseases.

What condition is associated with EP300 p.Pro882Arg (c.2645C>G)?

EP300 p.Pro882Arg (c.2645C>G) is associated with Inborn genetic diseases, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (ClinVar).

How common is EP300 p.Pro882Arg (c.2645C>G) in the general population?

EP300 p.Pro882Arg (c.2645C>G) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about EP300 p.Pro882Arg (c.2645C>G)?

AlphaMissense predicts likely benign (score 0.1226) — an in-silico prediction, not a clinical call.

EP300 p.Pro882Arg

c.2645C>G · rs772707021 · VCV1691054

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1226 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1226	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -9.43	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 6	GERP 2.5, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 11 kb · p 0.024 · regional, not allelic
Overall
CADD	23.6	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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00787% 127/1,613,912 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
Remaining individualsnot grpmax-eligible	0.0256%	3,905
Admixed American	0.0233%	4,285
African / African-American	0.00935%	10,700
European (non-Finnish)	0.0072%	13,883
Finnishnot grpmax-eligible	0.00313%	31,955

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.Pro882Arg
Coding: c.2645C>G
MANE Select: NM_001429
dbSNP: rs772707021
Type: single nucleotide variant
Location: chr22:41150026 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 882: 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 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
EP300 p.Arg1462Ter 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-pro882arg (accessed [today's date]).

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