ACE p.Pro1180=
c.3540G>A · rs376216920 · VCV2966865
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 -8.9 | GERP -3.7 |
| Overall | ||
| CADD | 0.08 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,060 alleles
Filtering AF
0.00623%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00467%
Overall
0.00273%
44/1,613,208 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,030 |
| African / African-American | 0.012% | 8,338 |
| East Asian | 0.00668% | 14,960 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,832 |
| Admixed American | 0.00333% | 30,012 |
| European (non-Finnish) | 0.00203% | 49,168 |
| South Asian | 0.0011% | 91,088 |
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.Pro1180=
- Coding
- c.3540G>A
- MANE Select
- NM_000789
- dbSNP
- rs376216920
- Type
- single nucleotide variant
- Location
- chr17:63496834 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.38 · 97 PDB
- Residue 1180
- an α-helix; the peptidase m2 2 domain
Similar variants
- ACE p.Pro1180Leu Uncertain significance ★ ⚠ same residue
- ACE p.Pro1180Val 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
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-pro1180 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown