KIT p.Lys499=
c.1497G>A · rs374432699 · VCV458876
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00305%, nfe)
Conditions
2
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 8.7 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 12.45 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00305%
European (non-Finnish) · 36/1,180,024 alleles
Filtering AF
0.00223%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00198%
Overall
0.00223%
36/1,614,064 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.Lys499=
- Coding
- c.1497G>A
- MANE Select
- NM_000222
- dbSNP
- rs374432699
- Type
- single nucleotide variant
- Location
- chr4:54726007 (GRCh38)
- Gene constraint
- LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.52 · 65 PDB
- Residue 499
- a β-strand; the ig-like c2-type 5 domain
Similar variants
- KIT p.Lys499Glu Uncertain significance ★ same residue
- KIT p.Lys499fs Pathogenic ★ same residue
- 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
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-lys499 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown