NM_005343.4:c.403C>G (p.Arg135Gly) is a missense variant in HRAS, a RASopathy gene. Only one criterion is met: PP2 at supporting strength, which applies to all RASopathy missense variants per the ClinGen RASopathy VCEP specification.¹ This variant is present in gnomAD v4.1 at extremely low frequency (2/1,613,606 alleles, AF ~0.00012%), with single alleles observed in South Asian and European (non-Finnish) populations. It is absent from gnomAD v2.1 and gnomAD-Canada.² This variant has been reported in ClinVar as Uncertain significance by a single clinical laboratory (GeneDx, VCID 3371962) with criteria provided. No expert panel review or pathogenic classification exists.³ Computational predictions are mixed: REVEL score 0.423 is intermediate, BayesDel score -0.136 leans benign, and SpliceAI predicts no splice impact (max delta 0.00). These do not converge on a consistent pathogenic or benign prediction.⁴ Position 135 is not within a VCEP-approved PM1 functional domain (P-loop residues 10-17; Switch I residues 25-40) and is not identified as a statistically significant hotspot by cancerhotspots.org.⁵ No functional studies have tested p.Arg135Gly in VCEP-approved assays (RAS Activation, MEK Activation, ERK Activation). The VCEP validation controls for HRAS are limited to G-domain residues (G12, G13, G60, K117, A146) and do not extend to position 135.⁶ No de novo occurrences, segregation data, or case-control studies exist for this variant. No literature publications were identified that mention this specific variant. With only PP2 (supporting) met and no other criteria fulfilled, this variant is classified as a Variant of Uncertain Significance (VUS) per the ACMG/AMP framework as modified by the ClinGen RASopathy VCEP.⁷