ACE p.Thr320=
c.960G>A · rs547724686 · VCV729345
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.379%, sas)
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 -4.8 | GERP -3.7 |
| Overall | ||
| CADD | 1.063 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.379%
South Asian · 345/91,072 alleles
Filtering AF
0.346%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.333%
Overall
0.0246%
397/1,613,900 alleles · rare
exomes 379/1,461,586 · genomes 18/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.379% | 264 |
| Middle Eastern | 0.033% | 3,029 |
| Remaining individualsnot grpmax-eligible | 0.0272% | 3,677 |
| African / African-American | 0.008% | 12,506 |
| East Asian | 0.00446% | 22,435 |
| European (non-Finnish) | 0.00212% | 47,201 |
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.Thr320=
- Coding
- c.960G>A
- MANE Select
- NM_000789
- dbSNP
- rs547724686
- Type
- single nucleotide variant
- Location
- chr17:63481580 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.38 · 97 PDB
- Residue 320
- an α-helix; 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-thr320 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown