Is KIT c.-5C>T pathogenic?

KIT c.-5C>T is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-06-25). Very rare (popmax 0.00551%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT c.-5C>T?

KIT c.-5C>T is associated with hereditary neoplastic syndrome (ClinVar).

How common is KIT c.-5C>T in the general population?

KIT c.-5C>T is very rare (popmax 0.00551%, nfe) (gnomAD).

KIT c.-5C>T

rs202070769 · VCV826116

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00551%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 0.86, phastCons 1
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00551% European (non-Finnish) · 65/1,179,670 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00404%

Overall 0.0044% 71/1,613,476 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00551%	18,149
Remaining individualsnot grpmax-eligible	0.0048%	20,817
Admixed American	0.00167%	60,002
Finnishnot grpmax-eligible	0.00156%	63,940
African / African-American	0.00134%	74,904

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.-5C>T
MANE Select: NM_000222
dbSNP: rs202070769
Type: single nucleotide variant
Location: chr4:54658010 (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

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

Similar variants

KIT p.Asp820Tyr Pathogenic ★★ same condition
KIT p.Leu576Pro Pathogenic/Likely 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
KIT c.1647+5C>A Uncertain significance ★★ same condition
KIT c.1647+5C>G Uncertain significance ★★ same condition
KIT c.1647+5C>T 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-minus-5c-t (accessed [today's date]).

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