C8B p.Ala461=
c.1383C>A · rs1644841427 · VCV3058059
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
C8B-related disorder
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 -0.33 | GERP -3.4, phastCons 0.015 |
| Overall | ||
| CADD | 3.918 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- C8B
- Protein
- p.Ala461=
- Coding
- c.1383C>A
- MANE Select
- NM_000066
- dbSNP
- rs1644841427
- Type
- single nucleotide variant
- Location
- chr1:56940864 (GRCh38)
- Gene constraint
- LOEUF 1.18 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.99 · 8 PDB
- Residue 461
- a UniProt-annotated variant site (in c8d2); the macpf domain; a β-strand
Disease context
C8B-related disorder
Similar variants
- C8B p.Ala461Ser Uncertain significance ★★ ⚠ same residue
- C8B p.Ala461Gly Uncertain significance ★ ⚠ same residue
- C8B p.Arg428Ter Pathogenic ★★ same condition
- C8B p.Cys508Ter Pathogenic/Likely pathogenic ★★ same condition
- C8B p.Gln91Ter Pathogenic/Likely pathogenic ★★ same condition
- C8B p.Arg121Ter Conflicting classifications of pathogenicity ★ same condition
- C8B p.Arg284Ter Pathogenic ★★ same type
- C8B p.Trp9Ter 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/c8b-p-ala461 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown