VariantForge: A Scalable REST Framework for Predicting Variant Impact via Grantham Distance

Grantham distance quantifies biochemical differences between amino acids, helping assess the functional impact of genetic variants. However, tools for batch analysis and workflow integration are scarce. VariantForge is an open-source REST API with a Svelte-based web interface that simplifies this process. It supports three use cases: (1) scoring single amino acid pairs, (2) computing sequence-wide distances between proteins, and (3) evaluating all possible amino acid substitutions from DNA variants. The API accepts both direct and batch inputs for high-throughput use. Benchmarks show consistency with curated datasets such as ClinVar. VariantForge is containerized via Docker for easy deployment and reproducibility, with a modular design that allows future integration of other biochemical metrics. By improving accessibility and scalability, VariantForge helps researchers prioritize pathogenic variants and investigate evolutionary constraints in protein-coding sequences.