C8B p.Leu358=
c.1074C>A · rs149848224 · VCV1462279
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00833%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.26 | donor loss, 31 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.25 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.71 | GERP -4.1, phastCons 0.058 |
| Overall | ||
| CADD | 1.835 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00833%
Admixed American · 5/60,004 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00236%
Overall
0.00297%
48/1,613,946 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00833% | 12,001 |
| European (non-Finnish) | 0.00356% | 28,095 |
| African / African-American | 0.00134% | 74,900 |
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.Leu358=
- Coding
- c.1074C>A
- MANE Select
- NM_000066
- dbSNP
- rs149848224
- Type
- single nucleotide variant
- Location
- chr1:56945852 (GRCh38)
- Gene constraint
- LOEUF 1.18 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.99 · 8 PDB
- Residue 358
- a UniProt-annotated variant site (in c8d2); a β-strand; the macpf 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-leu358 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown