Is EP400 p.Pro34= (c.102A>C) pathogenic?

EP400 p.Pro34= (c.102A>C) is classified Likely benign in EP400 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-04-13). Common (popmax 5.07%, mid) — too common for a highly-penetrant pathogenic allele; Associated with EP400-related disorder.

What condition is associated with EP400 p.Pro34= (c.102A>C)?

EP400 p.Pro34= (c.102A>C) is associated with EP400-related disorder (ClinVar).

EP400 p.Pro34=

Q: How common is EP400 p.Pro34= (c.102A>C) in the general population?

EP400 p.Pro34= (c.102A>C) is common (popmax 5.07%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.102A>C · rs753102248 · VCV3033301

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 5.07%, mid) — 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 -2
Overall
CADD	0.936	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.07% Middle Eastern · 21/414 alleles

Filtering AF 3.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.11%

Overall 2.46% 4,142/168,690 alleles · common exomes 3,457/148,066 · genomes 685/20,624 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	5.07%	20
African / African-American	3.56%	28
Remaining individualsnot grpmax-eligible	3.35%	30
East Asian	3.18%	31
South Asian	3.08%	32
Admixed American	3.07%	33
Ashkenazi Jewishnot grpmax-eligible	2.48%	40
European (non-Finnish)	2.39%	42
Amishnot grpmax-eligible	1.41%	71
Finnishnot grpmax-eligible	0.81%	124

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.Pro34=
Coding: c.102A>C
MANE Select: NM_015409
dbSNP: rs753102248
Type: single nucleotide variant
Location: chr12:131960721 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Residue 34: 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-pro34 (accessed [today's date]).

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