Clinical-Grade Somatic Variant Interpretation Performance via a Rule-Constrained Large Language Model Framework (Oncology Logic-Informed Variant Evaluator)

Interpretation of somatic variants in clinical oncology requires integration of gene-specific biology, tumor context, and multiple evidence sources. Although large language models (LLMs) can assist variant interpretation, concerns remain regarding reproducibility, safety, and dependence on opaque model behavior. A rule-constrained LLM-based decision support framework, Oncology Logic-Informed Variant Evaluator (OLIVE), was developed and evaluated for somatic variant interpretation in a clinical molecular pathology service.