Is EP400 p.Ala513= (c.1539A>G) pathogenic?

EP400 p.Ala513= (c.1539A>G) is classified Likely benign in EP400 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-30). Rare (popmax 0.12%, eas); Associated with EP400-related disorder.

What condition is associated with EP400 p.Ala513= (c.1539A>G)?

EP400 p.Ala513= (c.1539A>G) is associated with EP400-related disorder (ClinVar).

How common is EP400 p.Ala513= (c.1539A>G) in the general population?

EP400 p.Ala513= (c.1539A>G) is rare (popmax 0.12%, eas) (gnomAD).

EP400 p.Ala513=

c.1539A>G · rs555250384 · VCV3035422

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.12%, eas)

Conditions

EP400-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 -0.1	GERP -3.1, phastCons 0.26
Overall
CADD	5.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.12% East Asian · 53/44,260 alleles

Filtering AF 0.094% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0848%

Overall 0.00351% 56/1,594,452 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.12%	835
Remaining individualsnot grpmax-eligible	0.00324%	30,884
Admixed American	0.00176%	56,804

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: EP400
Protein: p.Ala513=
Coding: c.1539A>G
MANE Select: NM_015409
dbSNP: rs555250384
Type: single nucleotide variant
Location: chr12:131981592 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)

Full EP400 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EP400-related disorder

Similar variants

EP400 p.Ala513Thr Uncertain significance ★ same residue
EP400 p.Gly2702Glu Uncertain significance ★ same condition
EP400 p.Lys1297Arg Uncertain significance ★ same condition
EP400 p.Ser45Pro Uncertain significance ★ same condition
EP400 p.Ser573Phe Uncertain significance ★ same condition
EP400 c.2680-3C>A Uncertain significance same condition
EP400 c.4110+2T>A Uncertain significance same condition
EP400 c.5584+1G>A 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/ep400-p-ala513 (accessed [today's date]).

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