EP400 p.Pro593=
c.1779G>A · rs147639500 · VCV776780
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.03%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | donor loss at this position · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.1 |
| Overall | ||
| CADD | 0.024 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.03%
African / African-American · 2,273/75,018 alleles
Filtering AF
2.93%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.88%
Overall
0.162%
2,618/1,614,096 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.03% | 33 |
| Remaining individualsnot grpmax-eligible | 0.213% | 470 |
| Admixed American | 0.148% | 674 |
| Middle Eastern | 0.132% | 758 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0473% | 2,115 |
| South Asian | 0.0143% | 7,007 |
| European (non-Finnish) | 0.00712% | 14,048 |
| East Asian | 0.00669% | 14,951 |
| Finnishnot grpmax-eligible | 0.00156% | 64,008 |
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.Pro593=
- Coding
- c.1779G>A
- MANE Select
- NM_015409
- dbSNP
- rs147639500
- Type
- single nucleotide variant
- Location
- chr12:131982328 (GRCh38)
- Gene constraint
- LOEUF 0.365 · pLI 1.00 (gnomAD)
- Residue 593
- the 'disordered' region
Similar variants
- EP400 p.Pro593Ala Uncertain significance ★ same residue
- EP400 p.Pro593Leu 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
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-pro593 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown