When variants of unknown significance (VUSs) are observed in individuals of Oceanian ancestry, their interpretation has been hindered by the underrepresentation (non-representation, really) of Oceanian peoples in public-facing databases describing alleles present in human populations. The OLaGA (Obesity, Lifestyle, and Genetic Adaptations; ōlaga meaning life in Gagana Sāmoa) Study Group are the custodians of a controlled-access database of variation observed in the whole-genome sequences of 1,285 research participants from Independent Samoa. This has enabled us to respond to inquiries from genetic counselors and medical geneticists about the allele frequencies of VUSs observed in individuals of Samoan ancestry, which has enabled the identification of determinants of disease and the elucidation of disease mechanisms. One example has been the discovery of a hypomorphic allele in ECHS1 that results in a short-chain enoyl-CoA hydratase deficiency. When this variant—which has an allele frequency of 0.17 in Samoans—occurs in tandem with rare heterozygous pathogenic ECHS1 alleles, the result is a potentially devastating disorder of valine catabolism. This discovery has led to the prevention of disability in multiple susceptible children in Oceania and highlights the inherent importance of research in marginalized communities, as well as raising questions about how to best navigate questions of data sovereignty, benefit inequities, and public health communication.