The KRAS c.178G>C (p.Gly60Arg) variant has been observed in somatic cancers in COSMIC and has been reported in ClinVar, where it is classified as Pathogenic including review by the ClinGen RASopathy expert panel.
clinvar ↗This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting rarity in population reference datasets.
gnomad_v2 ↗ gnomad_v4 ↗In a published functional study, this variant increased the active GTP-bound KRAS fraction, showed marked GAP resistance, and increased downstream MEK and ERK signaling relative to wild type, consistent with an activating effect; the RASopathy VCEP approved functional-study resource also supports use of multiple approved assay types for this variant.
PMID:20949621 ↗Computational evidence supports a damaging missense effect, with REVEL 0.938 above the KRAS PP3 threshold of 0.7 and a positive BayesDel score of 0.539464; SpliceAI shows a possible splice effect with a max delta score of 0.25, but no RNA evidence was identified.
spliceai ↗ cspec ↗
