NM_002944.2:c.6079G>A (p.Glu2027Lys) is a rare missense variant in the ROS1 gene, absent from all gnomAD population databases (v2.1, v4.1, gnomAD-Canada).¹ In silico analysis predicts a deleterious effect: REVEL score 0.923 (strongly pathogenic), BayesDel score 0.4228 (moderately pathogenic). SpliceAI predicts no splice impact (max delta 0.15).² This variant has been reported once in COSMIC (COSV107471754) as a somatic alteration and is classified as Uncertain Significance in ClinVar (VariationID 2443073, 1 submitter, no assertion criteria provided).³ No variant-specific functional studies, case-control data, segregation data, or de novo observations were identified. OncoKB reports Unknown Oncogenic Effect.⁴ Under generic ACMG/AMP 2015 criteria, this variant meets PM2 (supporting: absent from population databases) and PP3 (supporting: in silico prediction of deleterious effect). All other assessed criteria are not met or not applicable.⁵ With two supporting-level pathogenic criteria (PM2_supporting + PP3_supporting) and no benign criteria met, the evidence is insufficient to classify this variant as likely pathogenic. The variant remains a Variant of Uncertain Significance per ACMG/AMP 2015 classification rules (PMID:25741868).⁶