The Functional Annotation of Variants Online Resource (FAVOR), http://favor.genohub.org, is a whole genome variant annotation database and portal that provides comprehensive variant functional annotations of all possible variants across the genome. It can facilitate the analysis of whole-genome sequencing studies, support the interpretation of variant functional impacts, and help prioritize causal variants of diseases or traits. To support the growing popularity and expand the scope of FAVOR, we present here a substantial platform update. The new release features dramatically expanded annotations, a completely redesigned infrastructure powered by a newly implemented application programming interface (FAVOR-API), and a revamped web interface with advanced data-visualization capabilities and enhanced query performance. Key expansions include much more comprehensive variant annotations, including global, tissue- and cell-type-specific variant annotations; gene and protein annotations; support for both hg38 and hg19 reference genomes; and an interactive genome-browser for visualization of multi-faceted variant annotations. The updated platform also includes FAVOR-GPT, a large language model-powered interface for navigating the FAVOR database and interpreting results. FAVOR continues to evolve to keep pace with advances in research on interpreting the functional and phenotypic impact of genomic variation.