Structural stratification of GRIN2B and GRIN2A ligand-binding domain variants reveals two distinct mechanisms of receptor dysfunction

This working paper presents a convergent three-track structural analysis of pathogenic GRIN2B and GRIN2A variants using AlphaFold 3, applying ipSAE interface scoring, binding pocket volumetrics, and GNINA molecular docking across 525 predicted structures. The results are consistent with two structural response patterns: open-cleft stabilisation (E413G, D731N) and interface disruption (R682C, A716T). Which converge across all three independent tracks and may warrant functional characterisation for GoF/LoF classification in NMDA receptor-related neurodevelopmental disorders. This record is released as a working paper to establish scientific priority of the described findings and methodology. Primary data and analysis scripts are available upon reasonable request for validation purposes. Extended datasets and implementation protocols are available under a formal collaboration agreement.