Can Tabular In-Context Learners Generalize to Biomolecular Property Prediction?

Predicting biomolecular properties from limited labeled data is a central bottleneck in protein engineering and small-molecule design. As strong pretrained encoders now supply rich fixed-length representations, the difficulty has shifted from representation learning to building a data-efficient predictor for the few-shot regime. Tabular foundation models such as TabPFN and TabICL are unlikely candidates for this role: they are in-context learners pretrained on synthetic tables drawn from random causal graphs, a generative prior with no obvious correspondence to the processes that produce protein sequences or molecular graphs. That this tabular, causal inductive bias should transfer to biomolecular data at all is counter-intuitive, yet we find it does. Treating each method as a predictor-representation pair, we evaluate across two domains. We find that on protein fitness regression tasks these in-context learning models coupled with ESM Cambrian representations achieve or exceed state-of-the-art results on ProteinGym, and outperform task-specific supervised regressors on a diverse esterase catalytic activity dataset. For small-molecule classification with ECFP/RDKit descriptors, no single predictor-representation pairing dominates across TDC ADMET, MoleculeNet, FS-Mol, and DrugOOD, but they are competitive with the existing task-specific state-of-the-art. Crucially, on both protein and small-molecule few-shot tasks, these predictor-representation pairs offer strong performance. We conclude that tabular foundation models can be strong biomolecular predictors, but only when coupled with expressive representations.