Is EP300 p.Pro10Arg (c.29C>G) pathogenic?

EP300 p.Pro10Arg (c.29C>G) is classified Likely benign in EP300 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-04). AlphaMissense: likely pathogenic (0.6557); Ultra-rare (popmax 0.033%, mid); Associated with EP300-related disorder.

What condition is associated with EP300 p.Pro10Arg (c.29C>G)?

EP300 p.Pro10Arg (c.29C>G) is associated with EP300-related disorder (ClinVar).

How common is EP300 p.Pro10Arg (c.29C>G) in the general population?

EP300 p.Pro10Arg (c.29C>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about EP300 p.Pro10Arg (c.29C>G)?

AlphaMissense predicts likely pathogenic (score 0.6557) — an in-silico prediction, not a clinical call.

EP300 p.Pro10Arg

c.29C>G · rs764405219 · VCV3038262

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6557 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

EP300-related disorder

Computational evidence

Protein change
AlphaMissense	0.6557	likely pathogenic
REVEL	0.624	indeterminate
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.42 · regional, not allelic
Overall
CADD	26.5	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00254% 41/1,614,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
South Asian	0.011%	9,109
European (non-Finnish)	0.00237%	42,144
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Pro10Arg
Coding: c.29C>G
MANE Select: NM_001429
dbSNP: rs764405219
Type: single nucleotide variant
Location: chr22:41093033 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 10: the 'interaction with alx1' region; the 'disordered' region; the 'interaction with rora' region

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

Disease context

EP300-related disorder

Similar variants

EP300 p.Pro10Ser 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-pro10arg (accessed [today's date]).

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