Is EP400 p.Ser1808= (c.5424C>G) pathogenic?

EP400 p.Ser1808= (c.5424C>G) is classified Benign in EP400 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-21). Common (popmax 31.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with EP400-related disorder.

What condition is associated with EP400 p.Ser1808= (c.5424C>G)?

EP400 p.Ser1808= (c.5424C>G) is associated with EP400-related disorder (ClinVar).

EP400 p.Ser1808=

Q: How common is EP400 p.Ser1808= (c.5424C>G) in the general population?

EP400 p.Ser1808= (c.5424C>G) is common (popmax 31.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5424C>G · rs58319354 · VCV3056557

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 31.9%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.39	GERP -3
Overall
CADD	2.112	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.9% African / African-American · 23,923/75,010 alleles

Filtering AF 31.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 31.4%

Overall 4.9% 79,030/1,613,212 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	31.9%	3
Finnishnot grpmax-eligible	14.6%	7
East Asian	6.98%	14
Middle Eastern	6.47%	15
South Asian	5.68%	18
Remaining individualsnot grpmax-eligible	5.66%	18
Admixed American	3.7%	27
European (non-Finnish)	2.6%	38
Ashkenazi Jewishnot grpmax-eligible	2.34%	43

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.Ser1808=
Coding: c.5424C>G
MANE Select: NM_015409
dbSNP: rs58319354
Type: single nucleotide variant
Location: chr12:132029743 (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-ser1808 (accessed [today's date]).

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