Is EP400 p.His31Pro (c.92A>C) pathogenic?

EP400 p.His31Pro (c.92A>C) is classified Benign in EP400 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-25). Common (popmax 22%, eas) — too common for a highly-penetrant pathogenic allele; Associated with EP400-related disorder.

What condition is associated with EP400 p.His31Pro (c.92A>C)?

EP400 p.His31Pro (c.92A>C) is associated with EP400-related disorder (ClinVar).

EP400 p.His31Pro

Q: How common is EP400 p.His31Pro (c.92A>C) in the general population?

EP400 p.His31Pro (c.92A>C) is common (popmax 22%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.92A>C · rs777204667 · VCV3034027

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 22%, eas) — 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.
REVEL	0.252	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	phastCons 0.94
Regional constraint	o/e 0.71	unconstrained · MANE · 549 bp · p 5.4e-06 · regional, not allelic
Overall
CADD	14.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22% East Asian · 993/4,508 alleles

Filtering AF 20.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.4%

Overall 13.1% 14,697/112,468 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	22%	5
Middle Eastern	19.6%	5
Admixed American	19.2%	5
Remaining individualsnot grpmax-eligible	17.1%	6
European (non-Finnish)	14.5%	7
Ashkenazi Jewishnot grpmax-eligible	14%	7
South Asian	11.7%	9
African / African-American	11.3%	9
Amishnot grpmax-eligible	3.53%	28
Finnishnot grpmax-eligible	2.33%	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.His31Pro
Coding: c.92A>C
MANE Select: NM_015409
dbSNP: rs777204667
Type: single nucleotide variant
Location: chr12:131960711 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Residue 31: 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 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-his31pro (accessed [today's date]).

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