NM_001904.3:c.101_102delGAinsTT (p.Gly34Val) is an in-frame indel in exon 3 of CTNNB1, within the well-established β-catenin degron hotspot (PM1). This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases (PM2).¹ The variant is absent from ClinVar and has no germline classification from any reputable source.² OncoKB classifies this variant as Likely Oncogenic based on somatic cancer context; this does not constitute a germline pathogenicity assertion.³ No functional studies have been performed on the specific c.101_102delinsTT indel. The G34V protein change has been observed via SNV in somatic cancers (HCC, medulloblastoma) and demonstrates gain-of-function through impaired β-catenin degradation, but this mechanism does not clearly support germline loss-of-function pathogenicity for CTNNB1 syndrome (PS3 not met). SpliceAI predicts no significant splice impact (max delta score = 0.08), and REVEL/BayesDel scores are unavailable for this indel (PP3 not assessed).⁴ Two moderate criteria (PM1 + PM2) are met. Under ACMG/AMP 2015 combination rules, two moderate criteria alone do not reach the threshold for Likely Pathogenic (requires ≥3 moderate, or 1 strong + 1-2 moderate, or 2 moderate + ≥2 supporting). This variant is classified as a Variant of Uncertain Significance (VUS).⁵