Interpreting human genetic variation at atomic resolution.

Computational structural genomics enables atomic-resolution interpretation of human genetic variants, revealing their mechanisms of dysfunction with high precision.

• Why it matters: Understanding the functional impact of genetic variants is crucial for advancing genomic medicine, yet many variants remain difficult to interpret with current methods.
• What they did: The authors review how integrating models of gene products, biomolecular complexes, molecular dynamics, multi-omics data, and AI tools allows for detailed mechanistic insights into variants.
• The result: This approach facilitates accurate prediction of variant effects at atomic resolution and supports classification based on their dysfunction mechanisms, enhancing diagnostic and therapeutic strategies.