ACE p.Val589=
c.1767C>T · rs140086153 · VCV1595144
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0184%, amr)
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 -5.1 | GERP -3.4 |
| Overall | ||
| CADD | 4.979 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0184%
Admixed American · 11/59,940 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00786%
Overall
0.00254%
41/1,611,786 alleles · ultra-rare
exomes 33/1,459,580 · genomes 8/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0184% | 5,449 |
| African / African-American | 0.012% | 8,321 |
| East Asian | 0.00446% | 22,443 |
| South Asian | 0.0044% | 22,726 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,170 |
| European (non-Finnish) | 0.0011% | 90,761 |
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
- ACE
- Protein
- p.Val589=
- Coding
- c.1767C>T
- MANE Select
- NM_000789
- dbSNP
- rs140086153
- Type
- single nucleotide variant
- Location
- chr17:63484387 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.38 · 97 PDB
- Residue 589
- an α-helix; the peptidase m2 1 domain
Similar variants
- ACE c.1342+1G>T Likely pathogenic ★★ same type
- ACE c.1709+5G>C Pathogenic/Likely pathogenic ★★ same type
- ACE c.3503+1G>C Likely pathogenic ★★ same type
- ACE c.945+2T>G Likely pathogenic ★★ same type
- ACE p.Arg265Ter Pathogenic ★★ same type
- ACE p.Arg496Gln Likely pathogenic ★★ same type
- ACE p.Arg496Ter Pathogenic/Likely pathogenic ★★ same type
- ACE p.Arg508Ter Pathogenic ★★ 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/ace-p-val589 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown