Is EP300 p.Ala1064Val (c.3191C>T) pathogenic?

EP300 p.Ala1064Val (c.3191C>T) is classified Uncertain significance in EP300 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-27). AlphaMissense: ambiguous (0.5314); Very rare (popmax 8.47e-05%, nfe); Associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency.

What condition is associated with EP300 p.Ala1064Val (c.3191C>T)?

EP300 p.Ala1064Val (c.3191C>T) is associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (ClinVar).

How common is EP300 p.Ala1064Val (c.3191C>T) in the general population?

EP300 p.Ala1064Val (c.3191C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about EP300 p.Ala1064Val (c.3191C>T)?

AlphaMissense predicts ambiguous (score 0.5314) — an in-silico prediction, not a clinical call.

EP300 p.Ala1064Val

c.3191C>T · rs1195853173 · VCV2632213

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5314 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Computational evidence

Protein change
AlphaMissense	0.5314	ambiguous
REVEL	0.322	indeterminate
SaProt	LLR -7.34	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 8,337 bp · p 1.9e-14 · regional, not allelic
Overall
CADD	25.7	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 8.47e-05% European (non-Finnish) · 1/1,179,976 alleles

Overall 6.84e-05% 1/1,461,822 alleles · very rare

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.Ala1064Val
Coding: c.3191C>T
MANE Select: NM_001429
dbSNP: rs1195853173
Type: single nucleotide variant
Location: chr22:41155043 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 1064: an α-helix; the bromo domain

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 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-ala1064val (accessed [today's date]).

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