Is KIT p.Tyr418Ter (c.1253_1254insAA) pathogenic?

KIT p.Tyr418Ter (c.12531254insAA) is classified Pathogenic in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-28). Absent from gnomAD; Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Tyr418Ter (c.1253_1254insAA)?

KIT p.Tyr418Ter (c.1253_1254insAA) is associated with gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Tyr418Ter (c.1253_1254insAA) in the general population?

KIT p.Tyr418Ter (c.1253_1254insAA) 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 p.Tyr418Ter

c.1253_1254insAA · rs2475527014 · VCV2817055

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

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	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -0.73, phastCons 0.095

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
Protein: p.Tyr418Ter
Coding: c.1253_1254insAA
MANE Select: NM_000222
dbSNP: rs2475527014
Type: Insertion
Location: chr4:54723604 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 418: a β-strand; the ig-like c2-type 5 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.Tyr418= Likely benign ★★ same residue
KIT p.Cys12fs Pathogenic ★ same condition
KIT p.Lys735fs Pathogenic ★ same condition
KIT p.Pro37fs Pathogenic ★ same condition
KIT c.1879+18_1879+19insAAATTAATTAACCACTCATTCATCGACCTCCCCACCCCATCCAACATCTCCGCATGATGAAACTTTGGCTCACTCCTTGGCGC Uncertain significance ★ same condition
KIT c.2234-4_2234-3insT Likely benign ★ same condition
KIT c.2361+16_2361+17insTTAT Likely benign ★ same condition
KIT p.Ala621Thr Pathogenic/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-tyr418ter (accessed [today's date]).

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