Is KIT p.Asp816= (c.2448C>T) pathogenic?

KIT p.Asp816= (c.2448C>T) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2021-11-03). Absent from gnomAD v4.1; Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Asp816= (c.2448C>T)?

KIT p.Asp816= (c.2448C>T) is associated with gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Asp816= (c.2448C>T) in the general population?

KIT p.Asp816= (c.2448C>T) is absent from gnomAD v4.1 (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.Asp816=

c.2448C>T · rs886043371 · VCV286360

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Overall
CADD	12.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KIT
Protein: p.Asp816=
Coding: c.2448C>T
MANE Select: NM_000222
dbSNP: rs886043371
Type: single nucleotide variant
Location: chr4:54733156 (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.Asp816Gly Uncertain significance ★ ⚠ same residue
KIT p.Asp816Tyr Uncertain significance ★ ⚠ same residue
KIT p.Asp816Val Conflicting classifications of pathogenicity ★ ⚠ same residue
KIT p.Asp816fs Pathogenic ★ same residue
KIT p.Asp816His Pathogenic ★★ same residue
KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same condition
KIT p.Asp820Tyr 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-asp816 (accessed [today's date]).

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