← Lymphatic Malformation Variant Atlas

ARAF S214P

c.640T>C NM_001654.5 RAS-MAPK transition, gain of function

Cancer hotspot Recurrent missense variant. COSMIC COSV51691221, COSV51692725, COSV51695605
Population · gnomAD Not observed Absent from the population database, consistent with a somatic, non-inherited driver.
ClinVar Not in ClinVar no exact-match submission
Protein region linker between the RBD and kinase domain Residue 214 of ARAF. UniProt P10398
AlphaMissense likely pathogenic Pathogenicity score 0.99. Computational prediction, not clinical evidence.

Position in ARAF 1 catalogued

RBD (19–91)RBDProtein kinase (310–570)Protein kina…1606 aaS214P

Reported in CCLA

ISSVA subsetAllele fractionSources
CCLA GoF
PMID31263281

Pathway and targeted therapy

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

Open and recent trials (8 in vascular / lymphatic anomalies for trametinib)

Primary sources (1)

  1. ARAF recurrent mutation causes central conducting lymphatic anomaly treatable with a MEK inhibitor.
    Li D, March ME, Gutierrez-Uzquiza A, Kao C, Seiler C, Pinto E, Matsuoka LS, Battig MR, Bhoj EJ, Wenger TL, Tian L, Robinson N, Wang T, Liu Y, Weinstein BM, Swift M, Jung HM, Kaminski CN, Chiavacci R, Perkins JA, Levine MA, Sleiman PMA, Hicks PJ, Strausbaugh JT, Belasco JB, Dori Y, Hakonarson H. · Nat Med · 2019

Mentioned in 8 publications indexed by Europe PMC.

Cross-references

COSMIC COSV51691221COSMIC COSV51692725COSMIC COSV51695605 gnomAD · ARAF ClinVar · S214P OncoKB cBioPortal · ARAF VarSome UniProt · ARAF AlphaFold · ARAF