ABSTRACT (OVERALL) With the rapid increase in the number of potential variants being identified through whole genome sequencing technologies in patients with rare disorders, the challenge for geneticists is now to confirm that these variants are causative of the phenotype. This requires detailed assessment and annotation to separate the causative variant from those that are simple nonsignificant polymorphisms and sequencing or mapping errors. This is a complex problem to address requiring interdisciplinary approaches, detailed bioinformatic analysis, the generation of informative animal models, and a concerted effort to evaluate the variants. Accomplishing this goal is frequently beyond what an individual lab can easily or efficiently accomplish. In this regard, the Center for Clinical and Translational Science and the Precision Medicine Institute assembled a team of scientists and clinicians with expertise in basic research, computational and data sciences, human genetics, clinical diagnosis, and animal model generation to form the UAB Center for Precision Animal Modeling (C-PAM). The team has established a pipeline in which research and clinical community nominated variants will be thoroughly analyzed using an innovative bioinformatic toolkit generated by the C-PAM Bioinformatics Section. Selected variants will be modeled in animals by the C-PAM Disease Modeling Unit and the new models evaluated for human disease relevance by clinicians in the C-PAM Pre/Co-clinical Section. Once generated, C-PAM established collaborations will utilize the detailed informatic analyses and the animal resource that will be distributed through the C-PAM Resource and Services Section to advance our understanding of disease pathogenesis, to ascertain efficacy of novel or repurposed therapeutics, and to contribute to improved human health. C-PAM will leverage and organize our already existing expertise to fulfill our vision to become a national resource for efficient and cost-effective analysis of pathogenicity of gene variants identified in patients with rare disorders and to produce informative animal models to pursue disease mechanisms and targeted therapeutics.