Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.87%, afr)
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 -0.004 | GERP 0.57 |
| Overall | ||
| CADD | 0.508 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.87%
African / African-American · 1,402/74,996 alleles
Filtering AF
1.79%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.76%
Overall
0.101%
1,633/1,613,692 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.87% | 53 |
| Admixed American | 0.175% | 571 |
| Remaining individualsnot grpmax-eligible | 0.128% | 781 |
| Middle Eastern | 0.033% | 3,031 |
| European (non-Finnish) | 0.00348% | 28,773 |
| South Asian | 0.00329% | 30,355 |
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.Val42=
- Coding
- c.126C>G
- MANE Select
- NM_000611
- dbSNP
- rs2231458
- Type
- single nucleotide variant
- Location
- chr11:33717413 (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 42
- the upar/ly6 domain; a β-strand; a disulfide bond
Similar variants
- CD59 p.Val42Ile Uncertain significance ★ ⚠ same residue
- CD59 p.Val42fs Pathogenic same residue
- 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
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-val42 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown