Is KIT p.Asp165Phe (c.493_494delinsTT) pathogenic?

KIT p.Asp165Phe (c.493494delinsTT) is classified Uncertain significance in KIT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-25). Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Asp165Phe (c.493_494delinsTT)?

KIT p.Asp165Phe (c.493_494delinsTT) is associated with gastrointestinal stromal tumor, hereditary neoplastic syndrome (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.Asp165Phe

c.493_494delinsTT · VCV3610285

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 3.5	GERP 0.44, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 3.4e-16 · regional, not allelic

Variant & gene context

Gene: KIT
Protein: p.Asp165Phe
Coding: c.493_494delinsTT
MANE Select: NM_000222
Type: Indel
Location: chr4:54698439 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 165: 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

Also linked: hereditary neoplastic syndrome

For Gastrointestinal stromal tumor (Orphanet):

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

Similar variants

KIT p.Asp165His Uncertain significance ★★ ⚠ same residue
KIT p.Asp165= Likely benign ★★ same residue
KIT p.Asp165Asn Uncertain significance ★ ⚠ same residue
KIT p.Asp165Tyr Uncertain significance ★ ⚠ same residue
KIT p.Asp165Val Uncertain significance ★ ⚠ same residue
KIT p.Ala4Phe Uncertain significance ★★ same condition
KIT p.Ala909Leu Uncertain significance ★★ same condition
KIT p.Asp398_Val399delinsGluPhe Uncertain significance ★★ 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-asp165phe (accessed [today's date]).

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