NM_020975.5:c.2434del is a frameshift variant in exon 14 of 20, predicted to cause a premature termination codon (p.Leu812CysfsTer57) and trigger nonsense-mediated decay.¹ RET loss-of-function is an established disease mechanism for Hirschsprung disease, meeting PVS1 at very strong strength under ClinGen SVI PVS1 recommendations (PMC6185798).² The variant truncates the RET tyrosine kinase domain (aa 724-1016) at codon 868, removing the activation loop and C-terminal tail. This domain is a critical functional domain characterized in the literature, meeting PM1 at moderate strength. The variant is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0, meeting PM2 at moderate strength under generic ACMG allele frequency thresholds.³ No pathogenic benign criteria are met. The variant is absent from ClinVar, has no functional studies, and lacks segregation or case-control data.⁴ Under generic ACMG/AMP 2015 combination rules (Richards et al. 2015), 1 very strong criterion (PVS1) plus 2 moderate criteria (PM1, PM2) meets the threshold for Pathogenic classification.⁵