Is KIT p.Tyr146del (c.434ATT[1]) pathogenic?

KIT p.Tyr146del (c.434ATT[1]) is classified Uncertain significance in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Tyr146del (c.434ATT[1])?

KIT p.Tyr146del (c.434ATT[1]) is associated with gastrointestinal stromal tumor (ClinVar).

How is Gastrointestinal stromal tumor inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

KIT p.Tyr146del

c.434ATT[1] · VCV4717712

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.21	GERP -4.8

Variant & gene context

Gene: KIT
Protein: p.Tyr146del
Coding: c.434ATT[1]
MANE Select: NM_000222
Type: Microsatellite
Location: chr4:54698380 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 146: a β-strand; a disulfide bond; the ig-like c2-type 2 domain

Full KIT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

gastrointestinal stromal tumor — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Gastrointestinal stromal tumor (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

KIT p.Tyr146= Likely benign ★★ same residue
KIT p.Tyr146Ter Pathogenic ★ same residue
KIT p.Tyr146Phe Uncertain significance ★ ⚠ same residue
KIT p.Glu562del Uncertain significance ★★ same condition
KIT c.2597-7_2597-6del Likely benign ★★ same condition
KIT c.756+22_756+24del Likely benign ★★ same condition
KIT p.Asp816fs Pathogenic ★ same condition
KIT p.Val29fs Pathogenic ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/kit-p-tyr146del (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown