Genotype, not variants: modeling recessive pathogenicity, with ABCA4-related retinopathy as an example

We propose a straightforward model for scoring the pathogenicity of the full set of gene copies in ABCA4- related retinopathy. The model works well in describing the only currently available time-independent descriptor of the severity of the disease: the age of onset. It provides a conceptual framework for understanding the genotypic underpinnings of the disease, with implications for genetic testing, planning therapeutic approach, and a heuristic quantitative description suitable for downstream modeling. It is also applicable to other recessive diseases in which the proteins encoded on different physical copies of the gene compete for a single resource, but are otherwise indistinguishable.