A method and computer system for identifying genes associated with a phenotype includes obtaining data representing mutations in a cohort of subjects exhibiting a phenotype. An evolutionary action (EA) score is calculated for each mutation using the data obtained. For each gene in the cohort, respective distributions of the calculated EA scores are determined for mutations found in the gene. The determined distributions of EA scores are quantitatively compared within the cohort and with random distributions to establish comparison data. Based on the comparison data, distributions of EA scores are identified that are non-random, and linkage of each gene in the cohort to the phenotype is assessed based on the identified non-random distributions to identify genes associated with the phenotype. The phenotype can be a disease, such as cancer, and linkage of each gene in the cohort to the disease can be assessed to identify disease causing genes.