ACE p.Pro1228=
c.3684G>A · rs201117207 · VCV3053437
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.594%, sas)
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 -1.6 | GERP -3.4 |
| Overall | ||
| CADD | 0.239 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.594%
South Asian · 538/90,646 alleles
Filtering AF
0.552%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.536%
Overall
0.0354%
570/1,610,124 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.594% | 168 |
| Remaining individualsnot grpmax-eligible | 0.0305% | 3,277 |
| Middle Eastern | 0.0206% | 4,864 |
| East Asian | 0.0134% | 7,466 |
| Admixed American | 0.00167% | 59,784 |
| African / African-American | 0.00134% | 74,884 |
| European (non-Finnish) | 0.000339% | 294,763 |
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.Pro1228=
- Coding
- c.3684G>A
- MANE Select
- NM_000789
- dbSNP
- rs201117207
- Type
- single nucleotide variant
- Location
- chr17:63496978 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.38 · 97 PDB
- Residue 1228
- a UniProt-annotated variant site (associated with high ace plasma levels; no effect on activity; increases secretion; rate of solubilization is 2.5-fold higher than wild-type); the 'juxtamembrane stalk' region
Similar variants
- ACE p.Pro1228Leu 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-pro1228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown