ACE p.Ser903=
c.2709G>A · rs537418583 · VCV324404
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0833%, amr)
Conditions
1
renal tubular dysgenesis
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 0.82 | GERP -3.2 |
| Overall | ||
| CADD | 5.201 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0833%
Admixed American · 50/60,024 alleles
Filtering AF
0.0648%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0583%
Overall
0.00427%
69/1,614,164 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0833% | 1,200 |
| Middle Eastern | 0.033% | 3,031 |
| African / African-American | 0.004% | 25,015 |
| East Asian | 0.00223% | 44,868 |
| South Asian | 0.0022% | 45,541 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,504 |
| European (non-Finnish) | 0.000847% | 118,004 |
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.Ser903=
- Coding
- c.2709G>A
- MANE Select
- NM_000789
- dbSNP
- rs537418583
- Type
- single nucleotide variant
- Location
- chr17:63491021 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.38 · 97 PDB
- Residue 903
- an α-helix; the peptidase m2 2 domain
Similar variants
- ACE p.Ser903Leu Uncertain significance ★ ⚠ same residue
- 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
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-ser903 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown