The c.6233C>G (p.Pro2078Arg) variant in USH2A was present in 0.4% (lower bound of the 95% CI of 50/10070) of Ashkenazi Jewish alleles in gnomAD v4. However, the next highest population frequency (aside from in the "remaining" group in gnomAD) was 0.002458% (29/1179812) of non-Finnish European alleles in gnomAD v4. Because this variant is likely a founder population in the AJ population, BS1 was downgraded to BS1_Supporting. The p.Pro2078Arg variant was detected in one proband with retinitis pigmentosa and the pathogenic variant in USH2A c.12067-2A>G but phase unknown (PM3_Supporting; Hadassah-Hebrew University Medical Center internal data, ClinVar SCV001161352.1, PMID:31456290). It has also been seen in at least 8 probands without a second variant identified in USH2A (Laboratory for Molecular Medicine, Invitae internal data, GeneDx, ClinVar SCV000201902.5, SCV001068267.2, SCV005078111.1). The REVEL computational prediction tool produced a score of 0.702, which is above the threshold necessary to apply PP3. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1_Supporting, PM3_Supporting, PP3 (ClinGen Hearing Loss VCEP specifications version 2; 1.15.2025).