C8B p.Pro92=
c.276C>T · rs138368595 · VCV788076
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.02%, sas)
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 -0.067 | GERP -4.6, phastCons 0.25 |
| Overall | ||
| CADD | 1.731 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.02%
South Asian · 1,838/91,074 alleles
Filtering AF
1.94%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.91%
Overall
0.128%
2,059/1,614,092 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 2.02% | 50 |
| Middle Eastern | 0.544% | 184 |
| Remaining individualsnot grpmax-eligible | 0.2% | 500 |
| East Asian | 0.0245% | 4,079 |
| Admixed American | 0.0117% | 8,574 |
| African / African-American | 0.008% | 12,505 |
| European (non-Finnish) | 0.00331% | 30,256 |
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.Pro92=
- Coding
- c.276C>T
- MANE Select
- NM_000066
- dbSNP
- rs138368595
- Type
- single nucleotide variant
- Location
- chr1:56956884 (GRCh38)
- Gene constraint
- LOEUF 1.18 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.99 · 8 PDB
- Residue 92
- a disulfide bond; a UniProt-annotated variant site (in c8d2); the tsp type-1 1 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-pro92 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown