NM_012289.4:c.44G>A (p.Arg15Gln) is a missense variant in exon 2 of KEAP1, a gene in which germline variants cause autosomal dominant familial multinodular goiter.¹ This variant is present at very low frequency in population databases (gnomAD v2.1: 0.0155%, 40/258,328 alleles; gnomAD v4.1: 0.0196%, 310/1,579,320 alleles) with no homozygotes observed. The overall frequency is below 0.1%, meeting PM2 at a supporting level. Note that the African/African American subpopulation frequency is 0.11%, borderline above the typical 0.1% threshold.² Multiple lines of computational evidence predict a benign effect: REVEL score 0.053, BayesDel score -0.511, and SpliceAI max delta 0.0, meeting BP4 at a supporting level.³ This variant has been reported once in COSMIC (COSV50285368) in a somatic cancer context and is classified as Uncertain significance in ClinVar by a single clinical laboratory (Ambry Genetics). OncoKB reports unknown oncogenic effect with no variant-specific functional evidence.⁴ No functional studies, segregation data, de novo reports, or case-control data are available for this variant. The variant does not lie in a mutational hotspot. The overall evidence profile includes one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4), consistent with a variant of uncertain significance. Additional evidence such as functional studies, segregation analysis, case-control data, or de novo observations would be needed to refine the classification.