Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.822%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.197 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -3 |
| Overall | ||
| CADD | 2.532 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.822%
African / African-American · 617/75,034 alleles
Filtering AF
0.769%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.747%
Overall
0.0468%
755/1,614,146 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.822% | 122 |
| Remaining individualsnot grpmax-eligible | 0.0656% | 1,524 |
| Admixed American | 0.035% | 2,857 |
| Middle Eastern | 0.033% | 3,030 |
| East Asian | 0.029% | 3,453 |
| Finnishnot grpmax-eligible | 0.0156% | 6,404 |
| South Asian | 0.00659% | 15,181 |
| European (non-Finnish) | 0.00381% | 26,222 |
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
- CD59
- Protein
- p.Asp74=
- Coding
- c.222C>T
- MANE Select
- NM_000611
- dbSNP
- rs2231460
- Type
- single nucleotide variant
- Location
- chr11:33710291 (GRCh38)
- Gene constraint
- LOEUF 1.277 · pLI 0.57 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.15 · 17 PDB
- Residue 74
- a disulfide bond; the upar/ly6 domain; an α-helix
Similar variants
- CD59 p.Cys89Tyr Pathogenic ★★ same type
- CD59 p.Met1Thr Likely pathogenic ★★ same type
- CD59 p.Ala50Val Uncertain significance ★★ ⚠ same type
- CD59 p.Arg78Cys Uncertain significance ★★ ⚠ same type
- CD59 p.Asn33Thr Uncertain significance ★★ ⚠ same type
- CD59 p.Asp92Asn Uncertain significance ★★ ⚠ same type
- CD59 p.Thr105Pro Uncertain significance ★★ ⚠ same type
- CD59 p.Val18Ile Uncertain significance ★★ ⚠ 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/cd59-p-asp74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown