RAD51C is an essential component of homologous recombination (HR) DNA repair, functioning as part of two distinct RAD51 paralog complexes: BCDX2 (RAD51B-RAD51C-RAD51D-XRCC2) and CX3 (RAD51C-XRCC3) 1. The BCDX2 complex orchestrates RAD51 nucleoprotein filament assembly on single-stranded DNA, stimulating both nucleation and extension of RAD51 filaments essential for double-strand break repair and replication fork protection 1. RAD51C exhibits coupled ATPase activity with RAD51B and contains a critical ATP-binding domain where deleterious missense variants cluster 2. The protein facilitates early HR stages including RAD51 foci formation and CHEK2 phosphorylation for damage signaling, while also participating in late-stage branch migration and Holliday junction resolution 3. Pathogenic RAD51C variants confer moderate breast cancer risk (OR=3.92) and high ovarian cancer risk (OR=14.8 for missense variants; OR=5.59 overall for truncating variants) 24. Cumulative risks to age 80 reach 21% for breast cancer and 11% for tubo-ovarian carcinoma in carriers 5. Homozygous RAD51C mutations cause Fanconi anemia complementation group O 3. Functional mapping of 9,188 variants achieved >99.9% classification accuracy, identifying hypomorphic alleles and resolving cancer-segregating variants 6.