Introduction: Although there have been significant advances in the genetic etiology of Parkinson’s disease (PD), most of this research has been conducted in European populations. This study aimed to characterize the genetic landscape of PD in South Africa.Methods: We recruited 689 PD probands across South Africa. These participants were genotyped using the NeuroBooster array in collaboration with the Global Parkinson’s Genetics Program (GP2). An in-house computational workflow was used to identify pathogenic missense variants. These were validated using Sanger sequencing. The CNV-Finder pipeline was used to screen for copy number variations (CNVs), which were validated using Multiplex Ligation-dependent Probe Amplification (MLPA). Previously identified pathogenic variants were used as positive controls in our analysis.Results: We identified 16 unique missense variants, confirming 15 with Sanger sequencing, in 47 individuals across seven well-established PD genes. Variants in GBA1 and PRKN were the most frequent. Additionally, 18 variants of unknown significance were found in known genes. Furthermore, seven new CNVs were identified, five in PRKN and two in SNCA, of which six were validated using MLPA. One of the CNVs was in the 5’ untranslated region of SNCA. When combining this data with previous findings, 3.5% of the probands have a genetic basis for their disease.Conclusions: We conducted the largest pathogenic variant screening to date in this unique and underrepresented population, and our findings highlight the rare contribution of known pathogenic variants. This study underscores the importance of expanding genetic research in African cohorts to improve global understanding of PD etiology.