Objective: Non-synonymous single nucleotide polymorphism (SNP) has a deleterious effect on the protein, thereby leading to a disease. Succinate dehydrogenase complex 5 (SDH5) gene, which encodes for a mitochondrial protein is responsible for the flavination of succinate dehydrogenase complex and also plays a major role in Krebs cycle. Mutations in this gene lead to the cancerous diseases such as paraganglioma and pheochromocytoma. The aim of this paper is to excavate the deleterious mutations in SDH5. Methods: The deleterious mutations in SDH5 are evaluated by assorted genomic algorithms and to find the drug binding affinity by docking the current drug against the mutated protein using molecular docking server. A total of 20 mutations were retrieved from SNP NCBI. The structural and the functional aspects of these 20 mutations were analyzed by using various genomics algorithms such as Sorting Intolerant From Tolerant, PolyPhen2.0, I-Mutant 2.0, SNPs, and gene ontology, protein analysis through evolutionary relationship, and prediction of human deleterious SNP, which helped us narrowing down our search to G78R and L80S as the deleterious missense mutations. The drug cyclophosphamide, used for the treatment of these cancerous diseases was considered for our study. Drug-protein interactions were studied using protein docking server. Binding efficiency of the cyclophosphamide drug with the most deleterious mutations were calculated. Result: G78R was found to be deleterious and confirmed that the mutation decrease the stability of the protein. Conclusion: Our findings lead to the better understanding of the deleterious mutations in SDH5, providing immense knowledge on the cancerous diseases, such as paraganglioma and pheochromocytoma, and drug docking mechanisms which will be extremely useful in the discovery of new treatments against such diseases. © 2015, Asian Journal of Pharmaceutical and Clinical Research. All rights reserved.