Is EP300 p.Arg1305Cys (c.3913C>T) pathogenic?

EP300 p.Arg1305Cys (c.3913C>T) is classified Uncertain significance in EP300 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-12). AlphaMissense: likely pathogenic (0.886); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EP300 p.Arg1305Cys (c.3913C>T)?

EP300 p.Arg1305Cys (c.3913C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EP300 p.Arg1305Cys (c.3913C>T) in the general population?

EP300 p.Arg1305Cys (c.3913C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about EP300 p.Arg1305Cys (c.3913C>T)?

AlphaMissense predicts likely pathogenic (score 0.886) — an in-silico prediction, not a clinical call.

EP300 p.Arg1305Cys

c.3913C>T · rs1555911073 · VCV546920

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.886	likely pathogenic
REVEL	0.8	moderately pathogenic-leaning
SaProt	LLR -12.36	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,843 bp · p 0.5 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.84e-05% 1/1,461,890 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.Arg1305Cys
Coding: c.3913C>T
MANE Select: NM_001429
dbSNP: rs1555911073
Type: single nucleotide variant
Location: chr22:41168487 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 1305: an α-helix; the cbp/p300-type hat domain

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.Asn2370Ser Uncertain significance ★★ ⚠ same condition
EP300 p.Gln1173Arg Uncertain significance ★★ ⚠ same condition
EP300 p.Gln2258Leu 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-arg1305cys (accessed [today's date]).

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