The KRAS c.508A>T (p.Met170Leu) variant has been reported in ClinVar and is classified there as uncertain significance, including an expert-panel submission from the ClinGen RASopathy Variant Curation Expert Panel.
clinvar ↗This variant is absent from gnomAD v2.1 and present at very low frequency in gnomAD v4.1 (10/1,611,476 alleles; AF 0.00062%), which is below the KRAS BA1 threshold of 0.05% and the BS1 threshold of 0.025%.
gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗RASopathy VCEP-approved KRAS functional assay classes are available, but no variant-specific approved functional result for p.(Met170Leu) was identified in the reviewed functional evidence, so functional pathogenic evidence was not applied.
Computational evidence supports a benign prediction because REVEL is 0.294, below the KRAS BP4 threshold of 0.3, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.04; BayesDel was 0.164958 as additional computational context.
spliceai ↗ cspec ↗
