C8B p.Cys590=
c.1770C>T · rs143486016 · VCV2054194
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0707%, 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 2.4 | GERP -3.8, phastCons 1 |
| Overall | ||
| CADD | 1.136 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0707%
African / African-American · 53/74,974 alleles
Filtering AF
0.0555%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0501%
Overall
0.00347%
56/1,612,152 alleles · ultra-rare
exomes 24/1,459,826 · genomes 32/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0707% | 1,415 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,334 |
| European (non-Finnish) | 0.00017% | 589,950 |
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
- C8B
- Protein
- p.Cys590=
- Coding
- c.1770C>T
- MANE Select
- NM_000066
- dbSNP
- rs143486016
- Type
- single nucleotide variant
- Location
- chr1:56929410 (GRCh38)
- Gene constraint
- LOEUF 1.18 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.99 · 8 PDB
- Residue 590
- the tsp type-1 2 domain; the 'disordered' region; a disulfide bond; a UniProt-annotated variant site (in c8d2)
Similar variants
- C8B p.Arg284Ter Pathogenic ★★ same type
- C8B p.Arg428Ter Pathogenic ★★ same type
- C8B p.Cys508Ter Pathogenic/Likely pathogenic ★★ same type
- C8B p.Gln91Ter Pathogenic/Likely pathogenic ★★ same type
- C8B p.Trp9Ter Pathogenic ★★ same type
- C8B p.Ala21Thr Uncertain significance ★★ ⚠ same type
- C8B p.Ala446Val Uncertain significance ★★ ⚠ same type
- C8B p.Ala461Ser 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/c8b-p-cys590 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown