Is KIT p.Asp816fs (c.2446_2447del) pathogenic?

KIT p.Asp816fs (c.24462447del) is classified Pathogenic in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-22). No gnomAD frequency available for this variant; Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Asp816fs (c.2446_2447del)?

KIT p.Asp816fs (c.2446_2447del) is associated with gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Asp816fs (c.2446_2447del) in the general population?

KIT p.Asp816fs (c.2446_2447del) is no gnomAD frequency available for this variant (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.Asp816fs

c.2446_2447del · rs2475571995 · VCV2770878

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

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	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 17 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.77, phastCons 1

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.Asp816fs
Coding: c.2446_2447del
MANE Select: NM_000222
dbSNP: rs2475571995
Type: Microsatellite
Location: chr4:54733151 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 816: the protein kinase domain; a UniProt-annotated variant site (in mastc; sporadic case; somatic mutation; constitutively activated and is much more rapidly autophosphorylated than wild type; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in a testicular tumor; seminoma; somatic mutation; constitutively activated); a UniProt-annotated variant site (in mastc; somatic mutation; constitutively activated; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in mastsys, mastc and mast cell leukemia; somatic mutation; constitutively activated; loss of interaction with mpdz); a UniProt-annotated variant site (in mastsys and mastc; also found in acute myeloid leukemia and a germ cell tumor of the testis; somatic mutation; constitutively activated)

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.Asp816Asn Uncertain significance ★★ ⚠ same residue
KIT p.Asp816= Conflicting classifications of pathogenicity ★ same residue
KIT p.Asp816Gly Uncertain significance ★ ⚠ same residue
KIT p.Asp816Tyr Uncertain significance ★ ⚠ same residue
KIT p.Asp816Val Conflicting classifications of pathogenicity ★ ⚠ same residue
KIT p.Asp816His Pathogenic ★★ same residue
KIT p.Glu562del Uncertain significance ★★ same condition
KIT c.2597-7_2597-6del Likely benign ★★ 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-asp816fs (accessed [today's date]).

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