ACE p.Leu200=
c.600G>A · rs4299 · VCV1545410
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.453%, 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 3.7 | GERP 0.053, phastCons 1 |
| Overall | ||
| CADD | 6.962 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.453%
African / African-American · 340/75,078 alleles
Filtering AF
0.413%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.398%
Overall
0.0237%
382/1,612,992 alleles · rare
exomes 171/1,460,608 · genomes 211/152,384 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.453% | 221 |
| Admixed American | 0.0466% | 2,144 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,682 |
| South Asian | 0.0011% | 91,088 |
| European (non-Finnish) | 0.000169% | 590,016 |
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.Leu200=
- Coding
- c.600G>A
- MANE Select
- NM_000789
- dbSNP
- rs4299
- Type
- single nucleotide variant
- Location
- chr17:63479857 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.38 · 97 PDB
- Residue 200
- an α-helix; the peptidase m2 1 domain
Similar variants
- ACE p.Leu200Pro 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-leu200 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown