Is EP300 p.Arg504Trp (c.1510C>T) pathogenic?

EP300 p.Arg504Trp (c.1510C>T) is classified Uncertain significance in EP300 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: ambiguous (0.4755); Very rare (popmax 0.000254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EP300 p.Arg504Trp (c.1510C>T)?

EP300 p.Arg504Trp (c.1510C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EP300 p.Arg504Trp (c.1510C>T) in the general population?

EP300 p.Arg504Trp (c.1510C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about EP300 p.Arg504Trp (c.1510C>T)?

AlphaMissense predicts ambiguous (score 0.4755) — an in-silico prediction, not a clinical call.

EP300 p.Arg504Trp

c.1510C>T · VCV3275608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4755 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4755	ambiguous
REVEL	0.554	indeterminate
SaProt	LLR -10.41	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 1.2, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 7,764 bp · p 0.0081 · regional, not allelic
Overall
CADD	24.7	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 0.000254% European (non-Finnish) · 3/1,180,030 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,850 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.Arg504Trp
Coding: c.1510C>T
MANE Select: NM_001429
Type: single nucleotide variant
Location: chr22:41131615 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 504: 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.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
EP300 p.Gln1173Arg 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-arg504trp (accessed [today's date]).

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