Through rare protein-altering variant association analysis, we find a missense variant in ANGPTL7 in UK Biobank (rs28991009, p.Gln175His, MAF = 0.8%, genotyped in 82,253 individuals with measured IOP and an independent set of 4,238 glaucoma patients and 250,660 controls) that significantly lowers IOP (β = -0.53 and -0.67 mmHg for heterozygotes, -3.40 and -2.37 mmHg for homozygotes, P = 5.96 x 10−9 and 1.07 x 10−13 for corneal compensated and Goldman-correlated IOP, respectively) and is associated with 34% reduced risk of glaucoma (P = 0.0062). The gene discussed is ANGPTL7; the disease is glaucoma.