Is KIT p.Glu562del (c.1681GAG[1]) pathogenic?

KIT p.Glu562del (c.1681GAG[1]) is classified Uncertain significance in KIT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-12). Very rare (popmax 8.47e-05%, nfe); Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Glu562del (c.1681GAG[1])?

KIT p.Glu562del (c.1681GAG[1]) is associated with gastrointestinal stromal tumor, hereditary neoplastic syndrome (ClinVar).

How common is KIT p.Glu562del (c.1681GAG[1]) in the general population?

KIT p.Glu562del (c.1681GAG[1]) is very rare (popmax 8.47e-05%, nfe) (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.Glu562del

c.1681GAG[1] · rs1722307508 · VCV937694

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 -4.7	GERP -5.1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,000 alleles

Overall 0.000205% 3/1,461,808 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,253
European (non-Finnish)grpmax	8.47e-05%	1,179,999

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: KIT
Protein: p.Glu562del
Coding: c.1681GAG[1]
MANE Select: NM_000222
dbSNP: rs1722307508
Type: Microsatellite
Location: chr4:54727449 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 562: a β-strand

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.Glu562Asp Uncertain significance ★ ⚠ same residue
KIT c.2597-7_2597-6del Likely benign ★★ same condition
KIT c.756+22_756+24del Likely benign ★★ same condition
KIT p.Asp816fs Pathogenic ★ same condition
KIT p.Val29fs Pathogenic ★ same condition
KIT p.Asn512del Uncertain significance ★ same condition
KIT p.Asp975del Uncertain significance ★ same condition
KIT p.Gly42fs Conflicting classifications of pathogenicity ★ ⚠ 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-glu562del (accessed [today's date]).

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