ACE p.Asp238=
c.714C>T · rs556856171 · VCV324368
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.066%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.30 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.33 | GERP -3.7, phastCons 0.009 |
| Overall | ||
| CADD | 13.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.066%
Middle Eastern · 4/6,062 alleles
Filtering AF
0.0225%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0135%
Overall
0.00254%
41/1,614,146 alleles · ultra-rare
exomes 36/1,461,822 · genomes 5/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.066% | 1,516 |
| Admixed American | 0.0117% | 8,575 |
| Finnishnot grpmax-eligible | 0.00938% | 10,663 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| South Asian | 0.00439% | 22,773 |
| African / African-American | 0.00266% | 37,529 |
| European (non-Finnish) | 0.00127% | 78,669 |
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.Asp238=
- Coding
- c.714C>T
- MANE Select
- NM_000789
- dbSNP
- rs556856171
- Type
- single nucleotide variant
- Location
- chr17:63480395 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.38 · 97 PDB
- Residue 238
- an α-helix; the peptidase m2 1 domain
Similar variants
- 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
- ACE p.Arg508Ter 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-asp238 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown