Is KIT p.Gln427Ter (c.1279C>T) pathogenic?

KIT p.Gln427Ter (c.1279C>T) is classified Likely pathogenic in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-03). Very rare (popmax 8.47e-05%, nfe).

How common is KIT p.Gln427Ter (c.1279C>T) in the general population?

KIT p.Gln427Ter (c.1279C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

KIT p.Gln427Ter

c.1279C>T · rs1306680919 · VCV620302

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 21
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,998 alleles

Overall 6.84e-05% 1/1,461,824 alleles · very rare

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.Gln427Ter
Coding: c.1279C>T
MANE Select: NM_000222
dbSNP: rs1306680919
Type: single nucleotide variant
Location: chr4:54723631 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 427: a β-strand; the ig-like c2-type 5 domain

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

Similar variants

KIT p.Gln427Arg Uncertain significance ★★ ⚠ same residue
KIT p.Gln427His Uncertain significance ★★ ⚠ same residue
KIT p.Gln427Leu Uncertain significance ★★ ⚠ same residue
KIT p.Gln427= Benign/Likely benign ★★ same residue
KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same type
KIT p.Asp816His Pathogenic ★★ same type
KIT p.Asp820Tyr Pathogenic ★★ same type
KIT p.Gln190Ter Pathogenic ★★ same type

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-gln427ter (accessed [today's date]).

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