Is EP300 p.Pro11Ser (c.31C>T) pathogenic?

EP300 p.Pro11Ser (c.31C>T) is classified Conflicting classifications of pathogenicity in EP300 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-06-22). AlphaMissense: likely benign (0.1353); Ultra-rare (popmax 0.0107%, afr); Associated with EP300-related disorder.

What condition is associated with EP300 p.Pro11Ser (c.31C>T)?

EP300 p.Pro11Ser (c.31C>T) is associated with EP300-related disorder, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (ClinVar).

How common is EP300 p.Pro11Ser (c.31C>T) in the general population?

EP300 p.Pro11Ser (c.31C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about EP300 p.Pro11Ser (c.31C>T)?

AlphaMissense predicts likely benign (score 0.1353) — an in-silico prediction, not a clinical call.

EP300 p.Pro11Ser

c.31C>T · rs762278198 · VCV2195143

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1353 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

EP300-related disorder

Computational evidence

Protein change
AlphaMissense	0.1353	likely benign
REVEL	0.402	indeterminate
SaProt	LLR -8.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.42 · regional, not allelic
Overall
CADD	23.5	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 0.0107% African / African-American · 8/74,932 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00273% 44/1,614,040 alleles · ultra-rare exomes 36/1,461,842 · genomes 8/152,198 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,367
Remaining individualsnot grpmax-eligible	0.0064%	15,620
European (non-Finnish)	0.00271%	36,876

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.Pro11Ser
Coding: c.31C>T
MANE Select: NM_001429
dbSNP: rs762278198
Type: single nucleotide variant
Location: chr22:41093035 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 11: the 'interaction with alx1' region; the 'disordered' region; the 'interaction with rora' region

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

Disease context

EP300-related disorder

Also linked: Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Similar variants

EP300 p.Pro11= 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-pro11ser (accessed [today's date]).

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