Is EP400 p.Ser573Phe (c.1718C>T) pathogenic?

EP400 p.Ser573Phe (c.1718C>T) is classified Uncertain significance in EP400 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). Absent from gnomAD v4.1; Associated with EP400-related disorder.

What condition is associated with EP400 p.Ser573Phe (c.1718C>T)?

EP400 p.Ser573Phe (c.1718C>T) is associated with EP400-related disorder (ClinVar).

How common is EP400 p.Ser573Phe (c.1718C>T) in the general population?

EP400 p.Ser573Phe (c.1718C>T) is absent from gnomAD v4.1 (gnomAD).

EP400 p.Ser573Phe

c.1718C>T · rs996419942 · VCV2632337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

EP400-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.392	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	GERP 0.58, phastCons 0.53
Regional constraint	o/e 0.95	unconstrained · MANE · 45 kb · p 0.17 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EP400
Protein: p.Ser573Phe
Coding: c.1718C>T
MANE Select: NM_015409
dbSNP: rs996419942
Type: single nucleotide variant
Location: chr12:131982267 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Residue 573: the 'disordered' region

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 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
EP400 p.Asn2615Ser 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-ser573phe (accessed [today's date]).

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