Here, we define the role of GRP94, the endoplasmic reticulum Hsp90 chaperone paralog, in managing alpha-1-antitrypsin deficiency on a residue-by-residue basis using Gaussian process regression-based machine learning to profile the spatial covariance relationships that dictate protein folding arising from sequence variants in the population. The gene discussed is HSP90AA1; the disease is hyperinsulinemic hypoglycemia, familial, 4.