Is KIT c.67+12C>T pathogenic?

KIT c.67+12C>T is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-03). Rare (popmax 0.12%, afr); Associated with mastocytosis.

What condition is associated with KIT c.67+12C>T?

KIT c.67+12C>T is associated with mastocytosis, piebaldism, gastrointestinal stromal tumor (ClinVar).

How common is KIT c.67+12C>T in the general population?

KIT c.67+12C>T is rare (popmax 0.12%, afr) (gnomAD).

KIT c.67+12C>T

rs374618962 · VCV901292

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.12%, afr)

Conditions

mastocytosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +12	near-intronic (+12 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.62	GERP 0.97, phastCons 0.005
Overall
CADD	10.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.12% African / African-American · 90/75,038 alleles

Filtering AF 0.0999% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0924%

Overall 0.00626% 101/1,613,226 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.12%	834
Remaining individualsnot grpmax-eligible	0.0144%	6,941
Admixed American	0.00333%	30,012

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
Coding: c.67+12C>T
MANE Select: NM_000222
dbSNP: rs374618962
Type: single nucleotide variant
Location: chr4:54658093 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB

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

Disease context

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

Also linked: piebaldism gastrointestinal stromal tumor

Similar variants

KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same condition
KIT p.Asp820Tyr Pathogenic ★★ same condition
KIT p.Gln190Ter Pathogenic ★★ same condition
KIT p.Leu576Pro Pathogenic/Likely pathogenic ★★ same condition
KIT p.Lys642Glu Pathogenic ★★ same condition
KIT p.Trp557Arg Pathogenic/Likely pathogenic ★★ same condition
KIT p.Val559Ala Pathogenic/Likely pathogenic ★★ same condition
KIT c.1232-3T>C 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-c-67-plus-12c-t (accessed [today's date]).

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