Is KIT p.Ser688fs (c.2062del) pathogenic?

KIT p.Ser688fs (c.2062del) is classified Pathogenic in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-09). Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Ser688fs (c.2062del)?

KIT p.Ser688fs (c.2062del) is associated with hereditary neoplastic syndrome (ClinVar).

KIT p.Ser688fs

c.2062del · VCV4645631

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary neoplastic syndrome

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 14 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.4	GERP 2.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: KIT
Protein: p.Ser688fs
Coding: c.2062del
MANE Select: NM_000222
Type: Deletion
Location: chr4:54729405 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 688: the protein kinase domain; an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KIT p.Ser688Thr Uncertain significance ★★ ⚠ same residue
KIT p.Ser688= Benign/Likely benign ★★ same residue
KIT p.Asp579del Pathogenic ★★ same condition
KIT p.Asn945fs Uncertain significance ★★ same condition
KIT p.Asp458_Val459del Uncertain significance ★★ same condition
KIT c.1990+1del Conflicting classifications of pathogenicity ★ ⚠ same condition
KIT c.925+5del Uncertain significance ★ same condition
KIT p.Arg740del 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-ser688fs (accessed [today's date]).

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