SNPnexus: an enhanced web platform for large-scale and multi-sample variant analysis (2025 update).

SNPnexus is a long-standing web-based platform for the functional annotation and prioritization of genetic variants. Since its previous release, SNPnexus has undergone substantial backend re-engineering resulting in major performance improvements and a complete restructuring of the underlying datasets. A redesigned interface now enables larger queries and multi-sample analysis enabling comparative workflows such as identifying shared pathogenic variants in disease cohorts and divergent mutations in cancer evolution studies. SNPnexus increased its capacity to 150 000 variants per query and introduced pre-annotation filters that allow users to restrict analyses to selected genes or genomic regions, improving efficiency while enabling targeted interrogation of high-priority targets. SNPnexus integrates updated and expanded annotations across both GRCh37 and GRCh38, covering genomic consequences, in silico pathogenicity predictions, population allele frequencies, evolutionary conservation, regulatory elements, biological pathways, and clinical associations. The refreshed result interface provides interactive visualizations for single-sample and cohort-level outputs, together with advanced filtering and export options. Optional user accounts now support query history and real-time job monitoring while preserving full, unregistered access for all users. SNPnexus remains free and open to all users without login requirements at https://snpnexus.org/.