Is KIT c.1540+2del pathogenic?

KIT c.1540+2del is classified Likely pathogenic in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-07). Absent from gnomAD; Associated with gastrointestinal stromal tumor.

What condition is associated with KIT c.1540+2del?

KIT c.1540+2del is associated with gastrointestinal stromal tumor (ClinVar).

How common is KIT c.1540+2del in the general population?

KIT c.1540+2del is absent from gnomAD (gnomAD).

How is Gastrointestinal stromal tumor inherited?

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

KIT c.1540+2del

rs2475537760 · VCV2036388

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Non-coding constraint	Z 1.97	1 kb window · o/e 0.85 · regional · uncalibrated

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: KIT
Coding: c.1540+2del
MANE Select: NM_000222
dbSNP: rs2475537760
Type: Deletion
Location: chr4:54726052 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB

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.Asn819fs Pathogenic ★★ same condition
KIT p.Asp579del Pathogenic ★★ same condition
KIT p.Asn945fs Uncertain significance ★★ same condition
KIT p.Asp458_Val459del Uncertain significance ★★ same condition
KIT c.1115+16del Benign/Likely benign ★★ same condition
KIT c.1116-16_1116-14del Likely benign ★★ same condition
KIT c.840_925+649del Likely pathogenic ★ same condition
KIT p.Ala273fs 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-c-1540-plus-2del (accessed [today's date]).

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