NM_006182.3:c.298G>A (p.Val100Met) is a missense variant in DDR2, a receptor tyrosine kinase gene in which missense variants cause spondylo-meta-epiphyseal dysplasia with short limbs and abnormal calcifications (SMED-SL).¹ This variant is extremely rare in population databases: absent from gnomAD v2.1 and present at 2/1,614,106 alleles (AF=1.24e−06) in gnomAD v4.1, with a grpmax filtering allele frequency of 2.8e−07, meeting PM2 at moderate strength.² In silico prediction tools support a deleterious effect: REVEL score 0.883 (strongly pathogenic), meeting PP3 at supporting strength.³ The variant is absent from ClinVar with no classifications from any submitter. No variant-specific functional data, de novo observations, or segregation information were available for assessment.⁴ Available evidence includes one moderate pathogenic criterion (PM2) and one supporting pathogenic criterion (PP3). No benign criteria are met. This evidence is insufficient to classify the variant as pathogenic or likely pathogenic under the ACMG/AMP 2015 framework. The variant is classified as a Variant of Uncertain Significance (VUS).⁵