Is EP300 p.Arg2317= (c.6951G>A) pathogenic?

EP300 p.Arg2317= (c.6951G>A) is classified Benign/Likely benign in EP300 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-01). Rare (popmax 0.923%, sas); Associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency.

What condition is associated with EP300 p.Arg2317= (c.6951G>A)?

EP300 p.Arg2317= (c.6951G>A) is associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency, colorectal cancer, Rubinstein-Taybi syndrome due to CREBBP mutations (ClinVar).

How common is EP300 p.Arg2317= (c.6951G>A) in the general population?

EP300 p.Arg2317= (c.6951G>A) is rare (popmax 0.923%, sas) (gnomAD).

EP300 p.Arg2317=

c.6951G>A · rs139551099 · VCV341828

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.923%, sas)

Conditions

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -0.92, phastCons 1
Overall
CADD	7.016	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.923% South Asian · 840/91,056 alleles

Filtering AF 0.871% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.85%

Overall 0.0863% 1,393/1,613,964 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.923%	108
East Asian	0.633%	158
Middle Eastern	0.181%	551
Remaining individualsnot grpmax-eligible	0.12%	833
European (non-Finnish)	0.015%	6,667
Admixed American	0.005%	19,995
African / African-American	0.004%	24,993

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.Arg2317=
Coding: c.6951G>A
MANE Select: NM_001429
dbSNP: rs139551099
Type: single nucleotide variant
Location: chr22:41178662 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 2317: the 'disordered' region

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

Also linked: colorectal cancer Rubinstein-Taybi syndrome due to CREBBP mutations Menke-Hennekam syndrome 2

Similar variants

EP300 p.Arg2317Gln Conflicting classifications of pathogenicity ★ ⚠ 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-arg2317 (accessed [today's date]).

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