C8B p.Ala11=
c.33G>A · rs766065295 · VCV1549401
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.448%, mid)
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 -9.9 | GERP -4.7 |
| Overall | ||
| CADD | 2.214 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.448%
Middle Eastern · 27/6,030 alleles
Filtering AF
0.316%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.272%
Overall
0.0127%
205/1,614,012 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.448% | 223 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,906 |
| South Asian | 0.0253% | 3,959 |
| Admixed American | 0.02% | 5,002 |
| European (non-Finnish) | 0.01% | 10,000 |
| African / African-American | 0.008% | 12,499 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00675% | 14,804 |
| East Asian | 0.00223% | 44,852 |
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.Ala11=
- Coding
- c.33G>A
- MANE Select
- NM_000066
- dbSNP
- rs766065295
- Type
- single nucleotide variant
- Location
- chr1:56965916 (GRCh38)
- Gene constraint
- LOEUF 1.18 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.99 · 8 PDB
Similar variants
- C8B p.Ala11Pro Uncertain significance ★ ⚠ same residue
- C8B p.Ala11Val Uncertain significance ★ ⚠ same residue
- 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
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-ala11 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown