NM_001904.4:c.802G>T (NP_001895.1:p.Gly268Ter) is a nonsense variant in exon 6 of 15 exons in CTNNB1, predicted to result in premature protein termination and nonsense-mediated decay of the transcript.¹ CTNNB1 loss-of-function is an established disease mechanism for autosomal dominant neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; MIM 615075), supported by ClinGen haploinsufficiency score of 3 and multiple publications describing pathogenic germline nonsense and frameshift variants.² This variant is absent from gnomAD v2.1 and v4.1 (0 alleles across >140,000 individuals) and absent from gnomAD-Canada v1.0, consistent with a rare pathogenic variant under strong purifying selection.³ The variant is not present in ClinVar, and no functional studies, cosegregation data, or detailed clinical phenotypes for individuals carrying this variant were available in the evidence record. Applying the generic ACMG/AMP 2015 classification framework (Richards et al. 2015, PMID:25741868), the combination of one very strong criterion (PVS1) and one moderate criterion (PM2) meets the threshold for Likely Pathogenic (1 Very Strong + 1 Moderate).⁴