C8B p.Arg296His
c.887G>A · rs781743688 · VCV1449184
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0763 | likely benign |
|---|---|---|
| REVEL | 0.53 | indeterminate |
| SaProt | LLR -8.57 | tolerated |
| ⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP 1.9, phastCons 0.94 |
| Regional constraint | o/e 1.09 | unconstrained · MANE · 37 kb · p 0.016 · regional, not allelic |
| Overall | ||
| CADD | 21.1 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0245% | 4,081 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,496 |
| African / African-American | 0.00534% | 18,724 |
| European (non-Finnish) | 0.0011% | 90,770 |
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.Arg296His
- Coding
- c.887G>A
- MANE Select
- NM_000066
- dbSNP
- rs781743688
- Type
- single nucleotide variant
- Location
- chr1:56946039 (GRCh38)
- Gene constraint
- LOEUF 1.18 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.99 · 8 PDB
- Residue 296
- a UniProt-annotated variant site (in c8d2); a β-strand; the macpf domain
Similar variants
- C8B p.Arg296Cys Uncertain significance ★★ ⚠ same residue
- C8B p.Ala21Thr Uncertain significance ★★ ⚠ same condition
- C8B p.Ala446Val Uncertain significance ★★ ⚠ same condition
- C8B p.Arg136Cys Uncertain significance ★★ ⚠ same condition
- C8B p.Arg136His Uncertain significance ★★ ⚠ same condition
- C8B p.Arg156Gly Uncertain significance ★★ ⚠ same condition
- C8B p.Arg428Gln Uncertain significance ★★ ⚠ same condition
- C8B p.Arg520Cys Uncertain significance ★★ ⚠ same condition
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-arg296his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown