NM_001174067.1:c.2242C>T (p.His748Tyr) is a missense variant in exon 17 of FGFR1, encoding the tyrosine kinase domain.¹ This variant is absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (genomes), meeting PM2 at a supporting level under generic ACMG/AMP thresholds.² No other pathogenic or likely pathogenic criteria were met. PVS1 is not applicable (missense, not a null variant). PS1 and PM5 could not be assessed because no pathogenic comparator missense at codon 748 was identified. PS3/BS3 were not met due to absence of variant-specific functional data; OncoKB reports 'Unknown Oncogenic Effect.' PS4 was not met because no case-control or cohort data exist. PP3/BP4 were not met due to equivocal in silico predictions (REVEL 0.648 vs. BayesDel 0.129). PP5/BP6 were not met because no reputable source has classified this specific variant, and the ClinVar match was to a different variant on a different transcript.³ With only one supporting pathogenic criterion (PM2) met and no benign criteria met, the variant does not reach a classifiable tier under ACMG/AMP 2015 combination rules. The evidence is insufficient to classify this variant as pathogenic, likely pathogenic, benign, or likely benign. The variant is therefore a Variant of Uncertain Significance (VUS).⁴