ACE p.Pro637=
c.1911G>A · rs200255554 · VCV2897968
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, 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 -3.7 | GERP -3.1 |
| Overall | ||
| CADD | 1.193 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
Middle Eastern · 1/5,340 alleles
Filtering AF
0.00334%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00302%
Overall
0.00403%
65/1,611,294 alleles · ultra-rare
exomes 61/1,459,020 · genomes 4/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0187% | 5,340 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,591 |
| Admixed American | 0.00501% | 19,946 |
| East Asian | 0.00446% | 22,417 |
| European (non-Finnish) | 0.00432% | 23,130 |
| African / African-American | 0.004% | 25,000 |
| South Asian | 0.0011% | 90,704 |
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.Pro637=
- Coding
- c.1911G>A
- MANE Select
- NM_000789
- dbSNP
- rs200255554
- Type
- single nucleotide variant
- Location
- chr17:63484531 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.38 · 97 PDB
- Residue 637
- a turn
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-pro637 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown