NM_000492.4:c.2723C>G (p.Thr908Ser) is a missense variant in exon 17 of CFTR, a gene in which both missense and loss-of-function variants are established disease mechanisms for cystic fibrosis and CFTR-related disorders.¹ This variant is present in gnomAD v4.1 at an extremely low allele frequency (2.48e-6; 4/1,613,954 alleles, 0 homozygotes) and is absent from gnomAD v2.1 and gnomAD-Canada v1.0, meeting PM2 at supporting strength.² Computational evidence is conflicting: REVEL score 0.557 is borderline, BayesDel score -0.037 is neutral, and SpliceAI max delta score 0.02 predicts no splicing impact; thus PP3 is not met and BP4 is not met.³ ClinVar classifies this variant as Uncertain significance based on a single clinical laboratory submission (GeneDx, SCV002549489, criteria provided, single submitter). No functional studies, segregation data, de novo observations, or case-control data were identified.⁴ With only one supporting pathogenic criterion (PM2) and no benign criteria met, the evidence is insufficient to meet thresholds for Likely Pathogenic or Likely Benign classification. The variant is classified as Uncertain significance per ACMG/AMP 2015 guidelines.⁵