Is EP400 p.Ser2816= (c.8448G>A) pathogenic?

EP400 p.Ser2816= (c.8448G>A) is classified Likely benign in EP400 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-31). Ultra-rare (popmax 0.0167%, amr); Associated with EP400-related disorder.

What condition is associated with EP400 p.Ser2816= (c.8448G>A)?

EP400 p.Ser2816= (c.8448G>A) is associated with EP400-related disorder (ClinVar).

How common is EP400 p.Ser2816= (c.8448G>A) in the general population?

EP400 p.Ser2816= (c.8448G>A) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

EP400 p.Ser2816=

c.8448G>A · rs144018934 · VCV3044700

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

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 -2.1	GERP -2.8
Overall
CADD	0.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/60,004 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00409% 66/1,612,658 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,000
African / African-American	0.012%	8,338
European (non-Finnish)	0.00364%	27,437
East Asian	0.00223%	44,876
South Asian	0.0022%	45,528
Remaining individualsnot grpmax-eligible	0.0016%	62,410

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.Ser2816=
Coding: c.8448G>A
MANE Select: NM_015409
dbSNP: rs144018934
Type: single nucleotide variant
Location: chr12:132064781 (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-ser2816 (accessed [today's date]).

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