Is KIT c.337+18del pathogenic?

KIT c.337+18del is classified Likely benign in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). Very rare (popmax 0.00161%, nfe); Associated with gastrointestinal stromal tumor.

What condition is associated with KIT c.337+18del?

KIT c.337+18del is associated with gastrointestinal stromal tumor (ClinVar).

How common is KIT c.337+18del in the general population?

KIT c.337+18del is very rare (popmax 0.00161%, nfe) (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.337+18del

rs1466139897 · VCV1659701

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +18	near-intronic (+18 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.63	GERP 0.091
Non-coding constraint	Z 1.36	1 kb window · o/e 0.91 · regional · uncalibrated
Overall
CADD	3.138	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,180,018 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00124% 20/1,614,058 alleles · very rare exomes 19/1,461,812 · genomes 1/152,246 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,106
Remaining individualsnot grpmax-eligible	0.0016%	62,488

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: KIT
Coding: c.337+18del
MANE Select: NM_000222
dbSNP: rs1466139897
Type: Deletion
Location: chr4:54695799 (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.1540+2del Likely pathogenic ★ same condition
KIT c.840_925+649del Likely 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-337-plus-18del (accessed [today's date]).

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