Is KIT p.Ile748fs (c.2244_2253del) pathogenic?

KIT p.Ile748fs (c.22442253del) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-04). Absent from gnomAD; Associated with piebaldism.

What condition is associated with KIT p.Ile748fs (c.2244_2253del)?

KIT p.Ile748fs (c.2244_2253del) is associated with piebaldism, hereditary neoplastic syndrome (ClinVar).

How common is KIT p.Ile748fs (c.2244_2253del) in the general population?

KIT p.Ile748fs (c.2244_2253del) is absent from gnomAD (gnomAD).

How is Piebaldism inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

KIT p.Ile748fs

c.2244_2253del · rs2109794937 · VCV1333929

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

piebaldism

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 16 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.35	GERP -2.2, phastCons 0.99

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.Ile748fs
Coding: c.2244_2253del
MANE Select: NM_000222
dbSNP: rs2109794937
Type: Deletion
Location: chr4:54731879 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 748: the protein kinase domain

Full KIT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

piebaldism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Piebaldism (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

KIT p.Ile748Val Uncertain significance ★★ ⚠ same residue
KIT p.Ile748Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
KIT p.Asp579del Pathogenic ★★ same condition
KIT p.Asn945fs Uncertain significance ★★ same condition
KIT p.Asp458_Val459del Uncertain significance ★★ same condition
KIT p.Asn80fs Pathogenic ★ same condition
KIT p.Met889fs Likely pathogenic ★ same condition
KIT p.Ser688fs 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-ile748fs (accessed [today's date]).

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