NM_001982.3:c.244G>A (p.Glu82Lys) is a missense variant in ERBB3 exon 3. This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada (0 alleles across all populations), meeting PM2 at moderate strength.¹ Multiple in silico predictors support a deleterious effect: REVEL score 0.948 (strongly pathogenic) and BayesDel score 0.443 (intermediate, leaning deleterious), meeting PP3 at supporting strength.² PVS1 is not applicable as c.244G>A is a missense variant, not a null variant (nonsense, frameshift, or canonical ±1,2 splice). Per ClinGen SVI PVS1 recommendations (PMC6185798), the generic PVS1 framework applies only to predicted null variants.³ The variant is absent from ClinVar, absent from COSMIC, and not located in a statistically significant mutational hotspot (CancerHotspots). No literature PMIDs were identified for this variant. OncoKB classifies it as 'Unknown Oncogenic Effect' without variant-specific functional evidence.⁴ No de novo, segregation, case-control, functional, or phenotype-specific data are available for this variant; PS2, PS3, PS4, PP1, PP4, PM6, and benign criteria BS2-BS4, BP5-BP6 remain not assessed. PM5 is not applicable as no pathogenic missense comparator at ERBB3 residue E82 was identified. BP7 is not applicable to missense variants.⁵ Overall classification: 1 moderate pathogenic criterion (PM2) and 1 supporting pathogenic criterion (PP3) are met. Under the generic ACMG/AMP 2015 combination rules (PMID:25741868), this does not reach the Likely Pathogenic threshold (minimum: 3 moderate, or 2 moderate + 2 supporting, or 1 moderate + 4 supporting). The variant is classified as a Variant of Uncertain Significance (VUS).⁶