ACE p.Asp218=
c.654C>T · rs151017978 · VCV2192645
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00836%, amr)
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 -3.1 | GERP -2.4 |
| Overall | ||
| CADD | 5.123 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00836%
Admixed American · 5/59,780 alleles
Filtering AF
0.00324%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.00261%
42/1,608,370 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00836% | 11,956 |
| South Asian | 0.0033% | 30,260 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,175 |
| African / African-American | 0.00267% | 37,435 |
| European (non-Finnish) | 0.00246% | 40,661 |
| East Asian | 0.00223% | 44,842 |
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.Asp218=
- Coding
- c.654C>T
- MANE Select
- NM_000789
- dbSNP
- rs151017978
- Type
- single nucleotide variant
- Location
- chr17:63479911 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.38 · 97 PDB
- Residue 218
- a turn; 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-asp218 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown