Inherited retinal dystrophies cause degeneration of the retina and progression to severe visual impairment. For patients to benefit from new therapeutic genetic approaches, their genetic variant/s need to be classified as pathogenic or likely pathogenic. Variants in RPGR are one of the most frequent causes of X-linked retinal dystrophy. We identified a retinal dystrophy family with a novel intronic variant in RPGR, which was classified as a variant of uncertain significance (VOUS). A unique RPGR isoform is exclusively expressed in the retina, raising the need for development of a model system derived from human cell types other than retina, since access to retinal tissue in humans is not easily available premortem. Fibroblasts from a patient with the novel RPGR variant were reprogrammed into iPSCs, and two clonal lines were differentiated into retinal pigment epithelial (RPE) cells and retinal organoids for disease modelling. qRT-PCR and immunostaining confirmed aberrant splicing, and decreased gene and protein expression in RPE cells, with mislocalisation along the transitional zone of the primary cilium. This allows reclassification of the variant to likely pathogenic, creating clinical utility. This work emphasises the value of iPSC-derived RPE as a viable model for pathogenicity and therapy studies of retinal ciliopathy genes.