EP400 p.Ala1547Val
c.4640C>T · rs771703326 · VCV2362409
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0228%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.163 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.97 | GERP 0.39, phastCons 0.004 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 6,210 bp · p 0.97 · regional, not allelic |
| Overall | ||
| CADD | 16.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0228%
Middle Eastern · 1/4,378 alleles
Filtering AF
0.0192%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0183%
Overall
0.017%
261/1,531,896 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0228% | 4,378 |
| European (non-Finnish) | 0.0214% | 4,675 |
| Remaining individualsnot grpmax-eligible | 0.0151% | 6,622 |
| African / African-American | 0.0055% | 18,194 |
| Admixed American | 0.00199% | 50,286 |
| South Asian | 0.0012% | 83,280 |
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.Ala1547Val
- Coding
- c.4640C>T
- MANE Select
- NM_015409
- dbSNP
- rs771703326
- Type
- single nucleotide variant
- Location
- chr12:132021271 (GRCh38)
- Gene constraint
- LOEUF 0.365 · pLI 1.00 (gnomAD)
- Residue 1547
- the 'disordered' region; a modified residue (phosphoserine)
Similar variants
- EP400 p.Ala1547Thr Uncertain significance ★ same residue
- 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
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-ala1547val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown