ACE p.Ala543=
c.1629C>T · rs141369597 · VCV2179346
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.064%, afr)
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 -0.33 | GERP 0.8, phastCons 0.05 |
| Overall | ||
| CADD | 7.609 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.064%
African / African-American · 48/75,024 alleles
Filtering AF
0.0495%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0444%
Overall
0.00347%
56/1,614,098 alleles · ultra-rare
exomes 19/1,461,846 · genomes 37/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.064% | 1,563 |
| Admixed American | 0.00833% | 12,003 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| European (non-Finnish) | 8.47e-05% | 1,180,032 |
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.Ala543=
- Coding
- c.1629C>T
- MANE Select
- NM_000789
- dbSNP
- rs141369597
- Type
- single nucleotide variant
- Location
- chr17:63483891 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.38 · 97 PDB
- Residue 543
- an α-helix; the peptidase m2 1 domain
Similar variants
- ACE p.Ala543Thr Uncertain significance ★ ⚠ same residue
- 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
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-ala543 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown