C8B p.Arg85=
c.255G>A · rs530181040 · VCV1285169
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.117%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.28 | acceptor loss at this position · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.17 | GERP -1.3, phastCons 0.99 |
| Overall | ||
| CADD | 3.563 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.117%
South Asian · 107/91,082 alleles
Filtering AF
0.0994%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0927%
Overall
0.00737%
119/1,614,054 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.117% | 851 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,501 |
| European (non-Finnish) | 0.000593% | 168,570 |
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.Arg85=
- Coding
- c.255G>A
- MANE Select
- NM_000066
- dbSNP
- rs530181040
- Type
- single nucleotide variant
- Location
- chr1:56956905 (GRCh38)
- Gene constraint
- LOEUF 1.18 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.99 · 8 PDB
- Residue 85
- a disulfide bond; a β-strand; the tsp type-1 1 domain
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-arg85 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown