C8B p.Ser250Arg
c.748A>C · rs768540351 · VCV1524489
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1357 | likely benign |
|---|---|---|
| REVEL | 0.024 | moderately benign-leaning |
| SaProt | LLR -8.80 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.4 | GERP -4.2 |
| Regional constraint | o/e 1.09 | unconstrained · MANE · 37 kb · p 0.016 · regional, not allelic |
| Overall | ||
| CADD | 8.453 | 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 |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| European (non-Finnish)grpmax | 0.0022% | 45,383 |
| African / African-American | 0.00133% | 74,942 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Ser250Arg
- Coding
- c.748A>C
- MANE Select
- NM_000066
- dbSNP
- rs768540351
- Type
- single nucleotide variant
- Location
- chr1:56949671 (GRCh38)
- Gene constraint
- LOEUF 1.18 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.99 · 8 PDB
- Residue 250
- a UniProt-annotated variant site (in c8d2); the macpf domain
Similar variants
- 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.Arg296Cys Uncertain significance ★★ ⚠ same condition
- C8B p.Arg296His Uncertain significance ★★ ⚠ same condition
- C8B p.Arg428Gln 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-ser250arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown