Is EP300 p.Ala2289Thr (c.6865G>A) pathogenic?

EP300 p.Ala2289Thr (c.6865G>A) is classified Likely benign in EP300 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: likely benign (0.0985); Very rare (popmax 0.00669%, eas); Associated with Inborn genetic diseases.

What condition is associated with EP300 p.Ala2289Thr (c.6865G>A)?

EP300 p.Ala2289Thr (c.6865G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EP300 p.Ala2289Thr (c.6865G>A) in the general population?

EP300 p.Ala2289Thr (c.6865G>A) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about EP300 p.Ala2289Thr (c.6865G>A)?

AlphaMissense predicts likely benign (score 0.0985) — an in-silico prediction, not a clinical call.

EP300 p.Ala2289Thr

c.6865G>A · rs1355958756 · VCV2523405

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0985 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0985	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -6.80	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 4	GERP -0.81, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 1,737 bp · p 6.7e-13 · regional, not allelic
Overall
CADD	24.3	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 0.00669% East Asian · 3/44,874 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000186% 3/1,613,824 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.Ala2289Thr
Coding: c.6865G>A
MANE Select: NM_001429
dbSNP: rs1355958756
Type: single nucleotide variant
Location: chr22:41178576 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 2289: 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

Similar variants

EP300 p.Ala2289= Benign ★ same residue
EP300 p.Arg1055Ter Pathogenic ★★ same condition
EP300 p.Arg1829Cys Likely pathogenic ★★ same condition
EP300 p.Gln1953Ter Likely pathogenic ★★ same condition
EP300 c.3590+4A>T Uncertain significance ★★ same condition
EP300 p.Ala627Val Uncertain significance ★★ ⚠ same condition
EP300 p.Arg1305Cys Uncertain significance ★★ ⚠ same condition
EP300 p.Asn2370Ser Uncertain significance ★★ ⚠ 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-ala2289thr (accessed [today's date]).

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