EP400 p.Pro1515Arg
c.4544C>G · rs141563140 · VCV2363237
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0559%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.685 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.6 | GERP 0.28, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 6,210 bp · p 0.97 · regional, not allelic |
| Overall | ||
| CADD | 23.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0559%
European (non-Finnish) · 659/1,179,698 alleles
Filtering AF
0.0523%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0509%
Overall
0.0437%
699/1,601,032 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0559% | 1,790 |
| Remaining individualsnot grpmax-eligible | 0.0465% | 2,151 |
| African / African-American | 0.00934% | 10,703 |
| Admixed American | 0.005% | 19,989 |
| Finnishnot grpmax-eligible | 0.00194% | 51,584 |
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.Pro1515Arg
- Coding
- c.4544C>G
- MANE Select
- NM_015409
- dbSNP
- rs141563140
- Type
- single nucleotide variant
- Location
- chr12:132021175 (GRCh38)
- Gene constraint
- LOEUF 0.365 · pLI 1.00 (gnomAD)
- Residue 1515
- the 'disordered' region
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-pro1515arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown