Is KIT p.Leu11fs (c.30dup) pathogenic?

KIT p.Leu11fs (c.30dup) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-09). Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Leu11fs (c.30dup)?

KIT p.Leu11fs (c.30dup) is associated with hereditary neoplastic syndrome, gastrointestinal stromal tumor (ClinVar).

KIT p.Leu11fs

c.30dup · VCV3720577

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	GERP 0.71, phastCons 1

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

Variant & gene context

Gene: KIT
Protein: p.Leu11fs
Coding: c.30dup
MANE Select: NM_000222
Type: Duplication
Location: chr4:54658040 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastrointestinal stromal tumor

Similar variants

KIT p.Leu11Phe Uncertain significance ★★ ⚠ same residue
KIT p.Leu11= Likely benign ★ same residue
KIT p.Leu707_Ser713dup Uncertain significance ★★ same condition
KIT p.Val422dup Uncertain significance ★★ same condition
KIT c.338-6dup Likely benign ★★ same condition
KIT c.67+5_67+18dup Likely benign ★★ same condition
KIT p.Ala597fs Pathogenic ★ same condition
KIT p.Arg588_Leu589insProGlnLeuProTyrAspHisLysTrpGluPheProArgAsnArg 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-p-leu11fs (accessed [today's date]).

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