Bridging Molecular AI Drug Discovery to Pan-Archipelagic Tripartite Genomic Stratification, Multi-Locus Hierarchical Wahlund Amplification, and Zero-Knowledge Deterministic Governance for National Orphan Drug Budgeting

As molecular artificial intelligence platforms—such as AlphaFold 3, AlphaMissense, and rational structural drug design engines—revolutionize atomic-level pathogenicity prediction and orphan therapeutic synthesis, translating these molecular breakthroughs into equitable national clinical deployment requires bridging the mathematical gap between microscopic protein dynamics, macro-archipelagic population genomics, and deterministic fiscal governance. Building upon our prior proofs of 1q21 GBA1/GBAP1 recombinant haplotype dynamics (DOI: 10.5281/zenodo.23581227), the 101x hierarchical Wahlund amplification in Japan's historical N=90 Gaucher disease cohort (DOI: 10.5281/zenodo.23581970), and pan-archipelagic tripartite genomic stratification (DOI: 10.5281/zenodo.23589190; Concept DOI: 10.5281/zenodo.23589189), this treatise formulates a unified tensor coupling molecular structural pathogenicity scores directly to a pan-archipelagic coalescent tensor across the tripartite ancestral structure of Japan (Paleolithic Jomon K1, Northeast Asian Yayoi K2, and East Asian Kofun K3). We map how macro-regional admixture variance and micro-topographic deme isolation interact across five major classes of rare genetic disorders in the Japanese archipelago: Gaucher disease (GBA1), Fukuyama Congenital Muscular Dystrophy (FKTN 3-kb SVA retrotransposon founder insertion), EYS-associated autosomal recessive retinitis pigmentosa, lysosomal storage disorders (GLB1, GAA, HEXA), and endemic foci of TTR V30M hereditary amyloidosis. Crucially, we prove (Theorem 3.1) that post-industrial rural depopulation deterministically amplifies local genetic drift (Wright's F_SD) and recessive disease incidence (dI/dt > 0) even when consanguineous marriage (F_IS -> 0) vanishes, while urbanization transiently converts homozygous founder clusters into pathogenic compound heterozygosity (Corollary 3.2). To ensure that autonomous or bureaucratic healthcare budgeting systems can never exploit genomic stratification or re-introduce age-based rationing—specifically Japan's "Age-18 Pediatric Subsidy Cliff" between the Child Welfare Act and the Intractable Diseases Act—we formalize a zero-knowledge fiscal state machine (QFS-zkVM) over the 64-bit Goldilocks prime field (F_p, p = 2^64 - 2^32 + 1). Governed by four mandatory hardware/cryptographic interlocks—RTO P2.0 side-channel zeroization, Q-SAFA quantum-safe consensus, PHOENIX_ROUTER pre-execution circuit breakers (<500 ns abort on any age-sensitivity Jacobian deviation, Theorem 5.1), and Human-in-Command (HIC)—this architecture guarantees lifelong therapeutic escrow and absolute patient genomic privacy under the Strict No-Learn Covenant (NLL-v1.0-2026).