Is EP300 p.Pro862Arg (c.2585C>G) pathogenic?

EP300 p.Pro862Arg (c.2585C>G) is classified Uncertain significance in EP300 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-23). AlphaMissense: likely benign (0.1597); Very rare (popmax 0.00267%, afr); Associated with EP300-related disorder.

What condition is associated with EP300 p.Pro862Arg (c.2585C>G)?

EP300 p.Pro862Arg (c.2585C>G) is associated with EP300-related disorder (ClinVar).

How common is EP300 p.Pro862Arg (c.2585C>G) in the general population?

EP300 p.Pro862Arg (c.2585C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about EP300 p.Pro862Arg (c.2585C>G)?

AlphaMissense predicts likely benign (score 0.1597) — an in-silico prediction, not a clinical call.

EP300 p.Pro862Arg

c.2585C>G · VCV3348300

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1597 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

EP300-related disorder

Computational evidence

Protein change
AlphaMissense	0.1597	likely benign
REVEL	0.487	indeterminate
SaProt	LLR -7.94	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 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 11 kb · p 0.024 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,016 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000205% 3/1,461,854 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,508
South Asian	0.0011%	91,072

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.Pro862Arg
Coding: c.2585C>G
MANE Select: NM_001429
Type: single nucleotide variant
Location: chr22:41149966 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 862: the 'disordered' region

Full EP300 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EP300-related disorder

Similar variants

EP300 p.Pro862Ala Uncertain significance ★★ ⚠ same residue
EP300 p.Arg1645Ter Pathogenic ★★ same condition
EP300 p.Arg200Ter Pathogenic/Likely pathogenic ★★ same condition
EP300 p.Phe1595Val Pathogenic/Likely pathogenic ★★ same condition
EP300 p.Arg1324Lys Uncertain significance ★★ ⚠ same condition
EP300 p.Asn301Asp Uncertain significance ★★ ⚠ same condition
EP300 p.Asn674Asp Uncertain significance ★★ ⚠ same condition
EP300 p.Gln570Arg 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-pro862arg (accessed [today's date]).

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