VARIANT: Web Server for Decoding and Analyzing Viral Mutations at Genome and Protein Levels

A comprehensive analysis of viral mutations is essential for understanding viral evolution, disease epidemiology, diagnosis, drug resistance, and immune escape. However, challenges remain in capturing complex mutation patterns and supporting diverse viral families with varying genome architectures. To address these challenges, we present VARIANT, an openly accessible web server for mutational analysis of RNA viral genomes and associated viral products across both single- and multi-segment virus genomes. The server takes as input a viral reference genome, a reference protein sequence, and/or multiple sequence alignment, and automatically provides full annotation of mutation types, including standard categories such as point mutations (missense, silent, and nonsense), insertions, deletions, and frameshift events in both coding and non-coding regions. In addition, VARIANT detects two biologically significant mutation patterns that are often overlooked by conventional software/packages: "row mutations", "hot mutations", and separately annotates potential programmed ribosomal frameshifting regions. The server currently contains automatic analysis of major viral pathogens, including SARS-CoV-2, HIV-1, Influenza H3N2, Ebola virus, and Chikungunya virus. It also allows users to analyze additional viruses by uploading custom genome information. Users can track VARIANT analysis progress in real time, visualize mutation distributions, and download structured results in ZIP format. VARIANT also incorporates dual graph topology analysis to classify frameshifting element structures from dot-bracket notation input. This feature enables systematic comparison of RNA secondary structure motifs across viral families by mapping structures to a comprehensive library of dual graph topologies. The web server is freely available at https://variant.up.railway.app/.