Is EP400 p.Ala30= (c.90C>G) pathogenic?

EP400 p.Ala30= (c.90C>G) is classified Likely benign in EP400 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-25). Very rare (popmax 0.00086%, nfe); Associated with EP400-related disorder.

What condition is associated with EP400 p.Ala30= (c.90C>G)?

EP400 p.Ala30= (c.90C>G) is associated with EP400-related disorder (ClinVar).

How common is EP400 p.Ala30= (c.90C>G) in the general population?

EP400 p.Ala30= (c.90C>G) is very rare (popmax 0.00086%, nfe) (gnomAD).

EP400 p.Ala30=

c.90C>G · rs2540894714 · VCV3058078

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00086%, nfe)

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 0.35	phastCons 0.99
Overall
CADD	8.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00086% European (non-Finnish) · 2/232,534 alleles

Filtering AF 0.000143% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000911% 3/329,446 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00712%	14,052
European (non-Finnish)grpmax	0.00086%	116,267

Ashkenazi Jewish 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.Ala30=
Coding: c.90C>G
MANE Select: NM_015409
dbSNP: rs2540894714
Type: single nucleotide variant
Location: chr12:131960709 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Residue 30: 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-ala30 (accessed [today's date]).

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