Oculocutaneous albinism type 2 (OCA-2, OMIM: 203200) is associated with variants in the OCA2 gene. In this study, we aimed to re-classify variants of uncertain significance (VUS) in OCA2 by evaluating subcellular localization and channel activity through multiplex assays of variant effect (MAVEs). Following the ClinGen guidelines for PS3 evidence, we selected 13 OCA2 variants from ClinVar (6 benign/likely benign [B/LB] and 7 pathogenic/likely pathogenic [P/LP]) for OddsPath analysis. The P/LP variants exhibited abnormal functions, while the B/LB variants demonstrated normal functions, supporting the application of "PS3_moderate" evidence for VUS re-classification. In our functional evaluation of 30 VUS identified in 38 individuals with suspected OCA-2 by trio whole-exome sequencing, we observed 6 VUS with abnormal localization and 11 with abnormal channel activity. Based on PS3_moderate evidence, 8 VUS were re-classified as LP, while 22 remained VUS. Consequently, 7 out of 38 previously undiagnosed patients received a molecular diagnosis of OCA-2. These MAVEs offer a robust approach for curating OCA2 VUS, enhancing diagnostic accuracy, and informing genetic counseling. Additionally, this variant cohort is a valuable resource for public databases.