NM_001034853.2(RPGR):c.1234C>T (p.Arg412Ter) is a nonsense variant that introduces a premature stop codon in exon 10 of 15, which is predicted to trigger nonsense-mediated decay (PVS1). This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_Supporting). At least one proband harboring this variant exhibits a phenotype including a family history consistent with X-linked inheritance showing no male-to-male transmission (2 pts) and female carriers showing milder symptoms (1 pt), night blindness (0.5 pts), visual acuity reduction (0.5 pts), myopia (0.5 pts), and non-recordable electroretinogram responses, with genotyping by whole exome sequencing panel identifying no alternative basis for retinal disease (2 pts), which together are specific for RPGR-related retinopathy (6.5 points, PMID: 32702353, PP4). This variant has been reported in at least 1 proband meeting one of the PS4 requirements of a male with some functional vision impairment by age 30 years and/or decreased or absent electroretinogram responses, or a female with functional visual abnormality and documentation of a male relative affected with retinitis pigmentosa, as well as a second apparently unrelated proband previously used for the PP4 code (PMID: 24938718, PMID: 34745198, PMID: 32702353, PS4_Supporting). The variant has been reported to segregate with retinal dystrophy through at least 2 affected meioses from at least 1 family (PP1; PMID: 24938718). In summary, this variant is classified as pathogenic for RPGR-related retinopathy based on the ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0; PVS1, PM2_Supporting, PP1, PP4, and PS4_Supporting.