Is EP400 p.Lys1402= (c.4206A>G) pathogenic?

EP400 p.Lys1402= (c.4206A>G) is classified Likely benign in EP400 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-27). Ultra-rare (popmax 0.0154%, sas); Associated with EP400-related disorder.

What condition is associated with EP400 p.Lys1402= (c.4206A>G)?

EP400 p.Lys1402= (c.4206A>G) is associated with EP400-related disorder (ClinVar).

How common is EP400 p.Lys1402= (c.4206A>G) in the general population?

EP400 p.Lys1402= (c.4206A>G) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

EP400 p.Lys1402=

c.4206A>G · rs772193706 · VCV3043371

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

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 -1.3	GERP -3.1
Overall
CADD	0.404	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0154% South Asian · 14/90,942 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00736%

Overall 0.00093% 15/1,613,236 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0154%	6,496
European (non-Finnish)	8.48e-05%	1,179,864

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.Lys1402=
Coding: c.4206A>G
MANE Select: NM_015409
dbSNP: rs772193706
Type: single nucleotide variant
Location: chr12:132018305 (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-lys1402 (accessed [today's date]).

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