ARAF (P10398) variants and mutations

ARAF (also known as P10398) is a human protein-coding gene encoding a serine/threonine-protein kinase A-Raf protein. It transmits RAS signals to the MEK-ERK pathway and participates in growth and developmental signaling. Activating germline or somatic variants can cause RASopathy phenotypes and have been identified as oncogenic drivers in selected tumors. This analysis covers 1,137 ARAF variants and mutations. Of these, 51% have computational variant effect predictions. Disease context includes cancer, Noonan syndrome, and Costello syndrome. Example ARAF variants include M1?, E2D, and E2G.

Variant analysis overview

Gene: ARAF
Protein: P10398
UniProt accession: P10398
Organism: Homo sapiens
Variants analyzed: 1137
Variant scope: all variants
Completed: 2026-08-21

Variant and mutation evidence

Variant composition: 908 unspecified-consequence records; 107 missense variants; 92 synonymous variants; 14 frameshift variants; 5 stop-gained variants; 5 splice-region variants; 5 in-frame deletions; 2 stop lost; 1 substitution
Prediction scores: 579 variants have prediction scores (51% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: cancer, Noonan syndrome, Costello syndrome, hypertrophic cardiomyopathy, low grade glioma, lymphatic malformation 12, glioma, colorectal adenocarcinoma, lung adenocarcinoma, small cell lung carcinoma, melanoma, lung carcinoma.

Protein structure and variant hotspots

Protein features: 2 domains; 10 binding sites; 9 post-translational modification sites.
Structural context: 457 variants have structural context.
PTM context: 32 variants overlap post-translational modification sites.
Experimental data: 67 protein positions have experimental scores. Source: binding assays.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable ARAF variants

Examples include M1?, E2D, E2G, P3S, P3P, P4R, P4S, R5Q. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

ARAF analysis run — ARAF (1,137 variants) — completed 2026-08-21