The c.6320G>A (NM_000350.3) variant in ABCA4 is a missense variant predicted to cause substitution of arginine by histidine at amino acid 2107; p.Arg2107His. The GroupMax filtering allele frequency in gnomAD v4.1.0 is 0.01986, which is greater than the ClinGen ABCA4 VCEP’s threshold for BS1 (>0.0163); however, this variant is listed on the BS1 exclusion list. The computational predictor REVEL gives a score of 0.88 which is above the threshold of >0.772, meeting PP3_Moderate. The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls with an OR of 6.1 and CI of 4.76-7.68, which is above the ABCA4 VCEP threshold of ≥5, where the CI does not contain 1 (PS4; PMID: 35120629). This variant has been detected in at least 2 individuals with ABCA4-related retinopathy. Of those individuals, 1 was compound heterozygous for the variant and a pathogenic or likely pathogenic variant but was not confirmed in trans (c.3523-1G>A; PMID: 9781034), and 1 individual was homozygous for the variant (PMID: 9781034) (PM3). Another missense variant, c.6319C>T; p.Arg2107Cys (ClinVar:635988), in the same codon has been classified as pathogenic for ABCA4-related retinopathy by the ClinGen ABCA4 VCEP, and Splice AI revealed no expected effects on splicing (PM5). ABCA4 expression in HEK293 cells showed relative protein expression of 0.90 +/- 0.17. However, ABCA4 ATPase activity in HEK293 cells showed decreased basal ATPase activity (0.66 +/- 0.13) indicating that this variant impacts protein function (PS3_Supporting; PMID 32845050). In summary, this variant meets the criteria to be classified as pathogenic for ABCA4-related retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen ABCA4 VCEP (Specification Version 1.0.0): PS4, PM3, PP3_Moderate, PM5 and PS3_Supporting.