Is EP300 p.Ser150Pro (c.448T>C) pathogenic?

EP300 p.Ser150Pro (c.448T>C) is classified Likely benign in EP300 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-13). AlphaMissense: likely benign (0.1457); Ultra-rare (popmax 0.0347%, afr); Associated with Inborn genetic diseases.

What condition is associated with EP300 p.Ser150Pro (c.448T>C)?

EP300 p.Ser150Pro (c.448T>C) is associated with Inborn genetic diseases, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (ClinVar).

How common is EP300 p.Ser150Pro (c.448T>C) in the general population?

EP300 p.Ser150Pro (c.448T>C) is ultra-rare (popmax 0.0347%, afr) (gnomAD).

What do computational predictors say about EP300 p.Ser150Pro (c.448T>C)?

AlphaMissense predicts likely benign (score 0.1457) — an in-silico prediction, not a clinical call.

EP300 p.Ser150Pro

c.448T>C · rs138241570 · VCV1591621

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1457 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0347%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1457	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.6	GERP -0.79, phastCons 0.5
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.42 · regional, not allelic
Overall
CADD	20.2	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 0.0347% African / African-American · 26/74,890 alleles

Filtering AF 0.0243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.00204% 33/1,614,004 alleles · ultra-rare exomes 16/1,461,872 · genomes 17/152,132 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0347%	2,880
Remaining individualsnot grpmax-eligible	0.008%	12,498
Admixed American	0.00333%	29,996

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.Ser150Pro
Coding: c.448T>C
MANE Select: NM_001429
dbSNP: rs138241570
Type: single nucleotide variant
Location: chr22:41117540 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 150: 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.Ser150Leu Uncertain significance ★ 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-ser150pro (accessed [today's date]).

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