Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Common
common (popmax 75.6%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
2
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 -4.1 | GERP -3.7 |
| Overall | ||
| CADD | 0.227 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
75.6%
African / African-American · 56,049/74,120 alleles
Filtering AF
75.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 74.9%
Overall
50.2%
807,435/1,608,750 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 75.6% | 1 |
| East Asian | 65% | 2 |
| Admixed American | 59.7% | 2 |
| South Asian | 58.8% | 2 |
| Remaining individualsnot grpmax-eligible | 50.8% | 2 |
| European (non-Finnish) | 47.5% | 2 |
| Finnishnot grpmax-eligible | 44.4% | 2 |
| Middle Eastern | 42.7% | 2 |
| Amishnot grpmax-eligible | 40.8% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 37.8% | 3 |
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.Thr776=
- Coding
- c.2328G>A
- MANE Select
- NM_000789
- dbSNP
- rs4343
- Type
- single nucleotide variant
- Location
- chr17:63488670 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.38 · 97 PDB
- Residue 776
- an α-helix; the peptidase m2 2 domain
Similar variants
- ACE p.Thr776Met 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-thr776 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown