vabase

KRAS A146T

c.436G>ANM_004985.512-25225628-C-T
RAS-MAPK gain of function transition Cancer hotspot ClinVar: Conflicting classifications of pathogenicity AlphaMissense: likely pathogenic CCLA

Reports 1 in CCLA

ISSVA entityAllele fractionSources
CCLA Li 2023: 3.9% (CLA163, single); Sheppard 2023: 3.3-3.4%

Position in KRAS 6 catalogued variants in this gene

Pathway and targeted therapy

Variant in the RAS-MAPK pathway. Repurposed drugs already used in the clinic for this pathway: trametinib and other MEK inhibitors.

Open and recent trials (3 in vascular / lymphatic anomalies for trametinib)

Primary sources 2

  1. Genomic profiling informs diagnoses and treatment in vascular anomalies.
    Li D, Sheppard SE, March ME, Battig MR, Surrey LF, Srinivasan AS, Matsuoka LS, Tian L, Wang F, Seiler C, Dayneka J, Borst AJ, Matos MC, Paulissen SM, Krishnamurthy G, Nriagu B, Sikder T, Casey M, Williams L, Rangu S, O'Connor N, Thomas A, Pinto E, Hou C, Nguyen K, Pellegrino da Silva R, Chehimi SN, Kao C, Biroc L, Britt AD, Queenan M, Reid JR, Napoli JA, Low DM, Vatsky S, Treat J, Smith CL, Cahill AM, Snyder KM, Adams DM, Dori Y, Hakonarson H. · Nat Med · 2023
  2. Lymphatic disorders caused by mosaic, activating KRAS variants respond to MEK inhibition.
    Sheppard SE, March ME, Seiler C, Matsuoka LS, Kim SE, Kao C, Rubin AI, Battig MR, Khalek N, Schindewolf E, O'Connor N, Pinto E, Priestley JR, Sanders VR, Niazi R, Ganguly A, Hou C, Slater D, Frieden IJ, Huynh T, Shieh JT, Krantz ID, Guerrero JC, Surrey LF, Biko DM, Laje P, Castelo-Soccio L, Nakano TA, Snyder K, Smith CL, Li D, Dori Y, Hakonarson H. · JCI Insight · 2023

Mentioned in 554 publications indexed by Europe PMC.

Annotations refreshed 2026-10-09 from Europe PMC, ClinVar, ClinicalTrials.gov, gnomAD, and Genome Nexus. Coordinates handled per assembly (gnomAD GRCh38, Genome Nexus GRCh37).