A Curated Pharmacogenomic Allele Catalog for Sub-Saharan African Populations

Sub-Saharan African populations carry pharmacogenomic alleles poorly represented in the European-derived reference panels underlying most clinical genotyping tools. We present a curated, machine-readable catalog of nine actionable alleles across six pharmacogenes ( CYP2D6 , CYP2B6 , CYP2C9 , CYP2C19 , CYP3A5 , NAT2 ) with African-specific frequency ranges, functional annotations, and evidence levels derived from reanalysis of 661 high-coverage whole-genome sequences across seven 1000 Genomes Project African populations. Direct comparison against PharmCAT v3.4.0 shows that CYP2D6 produces zero diplotype calls (0/661 samples callable) due to monomorphic reference positions absent from standard variant-only VCF output, a known limitation whose consequences for African allele carriers had not been reported. afripharmagen ’s reduced-position strategy identifies 243 CYP2D6 *17 and 134 CYP2D6 *29 carriers from the same input. For CYP2B6 , CYP2C9 , CYP2C19 , and NAT2 , both tools show concordance of 95–100%. Frequency gradients ( CYP2B6 *6: 30–50%; CYP2D6 *17: 15–35% in West Africa; CYP3A5 *1: 60–95%) translate directly into prescribing risk for efavirenz, tramadol, tacrolimus, and isoniazid. Pharmacogenomic decision support in African settings must incorporate population-specific allele definitions and input-format-aware strategies.