NM_004448.3:c.2506C>A (p.Leu836Met) is a missense variant in exon 21 of ERBB2. This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases (PM2_Supporting).¹ The variant is absent from ClinVar with no submissions or classifications reported.² In silico predictions are conflicting: REVEL (0.74) supports a deleterious effect, while BayesDel (0.21) does not and SpliceAI predicts no splicing impact (max delta = 0.00). Neither PP3 nor BP4 is met.³ OncoKB reports no variant-specific functional evidence (Unknown Oncogenic Effect) and no publications were identified that mention this variant.⁴ No CSPEC/VCEP framework exists for ERBB2; generic ACMG/AMP 2015 criteria were applied per Richards et al. (PMID:25741868). With only one supporting pathogenic criterion (PM2) and no benign criteria met, this variant is classified as a Variant of Uncertain Significance (VUS).⁵