NM_053056.3:c.517_519del (p.Glu173del) is an in-frame deletion of a single amino acid in exon 3 of CCND1. This variant is extremely rare in population databases (gnomAD v2.1: 1/250,946 alleles, AF = 0.00040%; gnomAD v4.1: 11/1,613,590 alleles, AF = 0.00068%), meeting PM2 at moderate strength.¹ As an in-frame deletion in a non-repeat region, the variant meets PM4 at moderate strength. The deletion removes Glu173, which lies within the cyclin C-terminal domain of CCND1.² CCND1 has no established germline disease association and no CSPEC/VCEP framework exists for this gene. The pvs1_gene_context literature review claimed CCND1 loss-of-function as a germline mechanism, but the supporting papers do not actually study CCND1 germline disease: PMID:41429883 concerns PEG10/Silver-Russell syndrome, PMID:42295563 concerns DSP cardiomyopathy, PMID:30352907 concerns somatic urothelial carcinoma, PMID:30573562 concerns MYCN, and PMID:32737004 concerns colorectal cancer therapy. None of these papers discuss CCND1 germline loss-of-function variants.³ Two moderate pathogenic criteria are met (PM2, PM4), with zero benign criteria. Under generic ACMG/AMP 2015 combination rules, this is insufficient for a Likely Pathogenic classification (which requires at least 2 moderate + 1 supporting, or 1 pathogenic + ≥2 pathogenic criteria). The variant is classified as a Variant of Uncertain Significance (VUS).⁴