Is EP300 p.Val486= (c.1458G>A) pathogenic?

EP300 p.Val486= (c.1458G>A) is classified Likely benign in EP300 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-08). Very rare (popmax 0.000339%, nfe); Associated with EP300-related disorder.

What condition is associated with EP300 p.Val486= (c.1458G>A)?

EP300 p.Val486= (c.1458G>A) is associated with EP300-related disorder (ClinVar).

How common is EP300 p.Val486= (c.1458G>A) in the general population?

EP300 p.Val486= (c.1458G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

EP300 p.Val486=

c.1458G>A · VCV3357166

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

EP300-related disorder

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 -0.067	GERP -5.9, phastCons 0.11
Overall
CADD	7.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,038 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,968 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)grpmax	0.000339%	295,010

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val486=
Coding: c.1458G>A
MANE Select: NM_001429
Type: single nucleotide variant
Location: chr22:41131563 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 486: 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.Val486Leu Uncertain significance ★★ ⚠ same residue
EP300 p.Val486Met Conflicting classifications of pathogenicity ★ ⚠ 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

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-val486 (accessed [today's date]).

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