Is EP300 c.3142+2T>A pathogenic?

EP300 c.3142+2T>A is classified Likely pathogenic in EP300 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-13). Absent from gnomAD v4.1; Associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency.

What condition is associated with EP300 c.3142+2T>A?

EP300 c.3142+2T>A is associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (ClinVar).

How common is EP300 c.3142+2T>A in the general population?

EP300 c.3142+2T>A is absent from gnomAD v4.1 (gnomAD).

EP300 c.3142+2T>A

VCV4723064

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.99	donor loss · deltas
Pangolin	Δ0.89	loss · gain 0.74 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1
Non-coding constraint	Z 0.06	1 kb window · o/e 1.00 · regional · uncalibrated
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EP300
Coding: c.3142+2T>A
MANE Select: NM_001429
Type: single nucleotide variant
Location: chr22:41152352 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB

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-c-3142-plus-2t-a (accessed [today's date]).

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