Is EP400 p.Glu440= (c.1320G>A) pathogenic?

EP400 p.Glu440= (c.1320G>A) is classified Likely benign in EP400 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-03-27). Very rare (popmax 0.00267%, afr); Associated with EP400-related disorder.

What condition is associated with EP400 p.Glu440= (c.1320G>A)?

EP400 p.Glu440= (c.1320G>A) is associated with EP400-related disorder (ClinVar).

How common is EP400 p.Glu440= (c.1320G>A) in the general population?

EP400 p.Glu440= (c.1320G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

EP400 p.Glu440=

c.1320G>A · rs960379455 · VCV3054001

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 3.9	phastCons 1
Overall
CADD	6.747	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,816 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000683% 11/1,611,606 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,408
Remaining individualsnot grpmax-eligible	0.0016%	62,406
European (non-Finnish)	0.000679%	147,369

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.Glu440=
Coding: c.1320G>A
MANE Select: NM_015409
dbSNP: rs960379455
Type: single nucleotide variant
Location: chr12:131961939 (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.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
EP400 p.Arg1295Ter 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-glu440 (accessed [today's date]).

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