Is EP300 p.Arg2263Gln (c.6788G>A) pathogenic?

EP300 p.Arg2263Gln (c.6788G>A) is classified Likely benign in EP300 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-23). AlphaMissense: likely benign (0.1948); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with EP300 p.Arg2263Gln (c.6788G>A)?

EP300 p.Arg2263Gln (c.6788G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EP300 p.Arg2263Gln (c.6788G>A) in the general population?

EP300 p.Arg2263Gln (c.6788G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about EP300 p.Arg2263Gln (c.6788G>A)?

AlphaMissense predicts likely benign (score 0.1948) — an in-silico prediction, not a clinical call.

EP300 p.Arg2263Gln

c.6788G>A · rs773841539 · VCV3031700

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1948 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1948	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -6.70	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 1,737 bp · p 6.7e-13 · regional, not allelic
Overall
CADD	24.0	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 0.00329% South Asian · 3/91,078 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000372% 6/1,613,768 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,359
European (non-Finnish)	0.000254%	393,326

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.Arg2263Gln
Coding: c.6788G>A
MANE Select: NM_001429
dbSNP: rs773841539
Type: single nucleotide variant
Location: chr22:41178499 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EP300 p.Arg2263Ter Pathogenic/Likely pathogenic ★★ 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-arg2263gln (accessed [today's date]).

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