Is EP400 p.Pro2509= (c.7527G>C) pathogenic?

EP400 p.Pro2509= (c.7527G>C) is classified Likely benign in EP400 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 20.9%, eas) — too common for a highly-penetrant pathogenic allele.

EP400 p.Pro2509=

Q: How common is EP400 p.Pro2509= (c.7527G>C) in the general population?

EP400 p.Pro2509= (c.7527G>C) is common (popmax 20.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7527G>C · rs749284192 · VCV769839

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 20.9%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	0.935	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.9% East Asian · 3,220/15,412 alleles

Filtering AF 20.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 20%

Overall 12.5% 54,093/434,382 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	25.1%	4
East Asiangrpmax	20.9%	5
Ashkenazi Jewishnot grpmax-eligible	18.8%	5
Middle Eastern	18.2%	6
Remaining individualsnot grpmax-eligible	17.1%	6
Admixed American	12.7%	8
European (non-Finnish)	11.8%	8
African / African-American	8.76%	11
South Asian	6.17%	16
Amishnot grpmax-eligible	4.47%	22

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro2509=
Coding: c.7527G>C
MANE Select: NM_015409
dbSNP: rs749284192
Type: single nucleotide variant
Location: chr12:132053396 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Residue 2509: an α-helix

Full EP400 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EP400 p.Thr664Ala Uncertain significance ★★ same type
EP400 c.1435+8G>A Benign ★★ same type
EP400 c.7027-9C>T Benign ★★ same type
EP400 p.Ala146= Likely benign ★★ same type
EP400 p.Ala1649Thr Benign/Likely benign ★★ same type
EP400 p.Ala1764= Benign ★★ same type
EP400 p.Ala244= Likely benign ★★ same type
EP400 p.Ala2803= Likely benign ★★ same type

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-pro2509 (accessed [today's date]).

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