FABIAN-variant 2026: improved prediction of the effects of DNA variants on transcription factor binding

Variants in promoters and enhancers can alter the binding of transcription factors (TFs), but their functional assessment remains difficult. FABIAN-variant is a web application that predicts the effects of DNA variants on TF binding by comparing position weight matrix (PWM) and transcription factor flexible model (TFFM) scores between reference and variant alleles. Here, we present FABIAN-variant 2026, a major update that expands the prediction model library from ~5000 to over 40 000 models for >1500 human TFs, sourced from nine PWM databases and including 1290 TFFMs. The application now supports the mouse genome (GRCm38 and GRCm39) with over 35 000 models for >1100 mouse TFs. An optional BPNet deep learning scorer provides neural network-based binding predictions for 240 human TFs. Known TF binding site information has been expanded from three to five sources. Predictions for over 1400 heterodimer TF complexes have been added. The web server has been rewritten in Rust and the scoring engine optimized, reducing runtime by ~70%. A RESTful JSON API and a standalone command-line version enable programmatic access and local high-throughput analysis. FABIAN-variant 2026 is available at https://fabianapp.org/variant26/. The web server is free and open to all users and there is no login requirement.