NM_024675.4:c.740C>G (p.Thr247Arg) is a missense variant in exon 4 of PALB2 identified in 1 of 1996 Australian familial breast cancer cases and 0 of 1998 cancer-free controls (Thompson et al. 2015).¹ Under the ClinGen PALB2 VCEP v1.2.0 framework, most pathogenic criteria are not applicable to missense variants: PVS1 (null variant only), PS1 (missense excluded), PM1 (missense excluded), PM5 (truncating only), PP2 (missense excluded), PP3/BP4 (missense excluded). PS3/BS3 are not applicable per VCEP.² BP1_Supporting is met: the PALB2 VCEP applies BP1 to all missense variants at Supporting level, reflecting the very low likelihood that missense variants in PALB2 are pathogenic based on published functional data.³ PM2 could not be assessed: gnomAD v4 frequency data is unavailable (scrape timed out). The variant has an rsID (rs587782658) and is present in population databases, but the exact allele frequency needed for the VCEP PM2_Supporting threshold (≤0.000333%) requires manual confirmation. PS4 is not met: the single case observation (1/1996 cases vs 0/1998 controls) does not constitute a statistically significant case-control enrichment (p=0.48, Fisher's exact test).⁴ No functional data (PS3 not applicable per VCEP), no segregation data (PP1/BS4 not assessed), no de novo reports (PS2/PM6 not applicable), and no Fanconi Anemia observations (BS2 not assessed) are available for this variant. In silico predictors are mixed: REVEL score 0.065 and BayesDel -0.512 are benign-leaning; SpliceAI delta 0.00 predicts no splice impact. However, under VCEP rules, PP3 and BP4 are not applicable for missense variants regardless of predictor scores.⁵ ClinVar classification is Uncertain significance (7 clinical laboratories) / Likely benign (1 laboratory), with no expert panel review. This is consistent with the limited evidence available for this missense variant.⁶