ACE p.Lys402=
c.1206G>A · rs568223557 · VCV892247
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.247%, mid)
Conditions
1
renal tubular dysgenesis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.8 | GERP 0.78, phastCons 1 |
| Overall | ||
| CADD | 9.663 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.247%
Middle Eastern · 15/6,062 alleles
Filtering AF
0.152%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.123%
Overall
0.00118%
19/1,614,118 alleles · rare
exomes 18/1,461,834 · genomes 1/152,284 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.247% | 404 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
| Admixed American | 0.00167% | 60,026 |
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.Lys402=
- Coding
- c.1206G>A
- MANE Select
- NM_000789
- dbSNP
- rs568223557
- Type
- single nucleotide variant
- Location
- chr17:63482553 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.38 · 97 PDB
- Residue 402
- the peptidase m2 1 domain
Similar variants
- ACE c.1709+5G>C Pathogenic/Likely pathogenic ★★ same condition
- ACE c.3503+1G>C Likely pathogenic ★★ same condition
- ACE p.Arg496Ter Pathogenic/Likely pathogenic ★★ same condition
- ACE p.Arg508Ter Pathogenic ★★ same condition
- ACE p.Arg791Ter Pathogenic ★★ same condition
- ACE p.Tyr266Ter Pathogenic/Likely pathogenic ★★ same condition
- ACE c.2739+5G>A Uncertain significance ★★ same condition
- ACE p.Ala730Glu Uncertain significance ★★ ⚠ same condition
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-lys402 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown