Is KIT p.Lys642Gln (c.1924A>C) pathogenic?

KIT p.Lys642Gln (c.1924A>C) is classified Uncertain significance in KIT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-23). AlphaMissense: likely pathogenic (0.9821); Absent from gnomAD v4.1; Associated with acute myeloid leukemia.

What condition is associated with KIT p.Lys642Gln (c.1924A>C)?

KIT p.Lys642Gln (c.1924A>C) is associated with acute myeloid leukemia, piebaldism, testicular germ cell tumor (ClinVar).

How common is KIT p.Lys642Gln (c.1924A>C) in the general population?

KIT p.Lys642Gln (c.1924A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIT p.Lys642Gln (c.1924A>C)?

AlphaMissense predicts likely pathogenic (score 0.9821) — an in-silico prediction, not a clinical call.

KIT p.Lys642Gln

c.1924A>C · rs121913512 · VCV2568309

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9821 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

acute myeloid leukemia

Computational evidence

Protein change
AlphaMissense	0.9821	likely pathogenic
REVEL	0.791	moderately pathogenic-leaning
SaProt	LLR -11.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.6, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 4,114 bp · p 4.1e-05 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KIT
Protein: p.Lys642Gln
Coding: c.1924A>C
MANE Select: NM_000222
dbSNP: rs121913512
Type: single nucleotide variant
Location: chr4:54728055 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 642: the protein kinase domain; an α-helix

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

Disease context

acute myeloid leukemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: piebaldism testicular germ cell tumor gastrointestinal stromal tumor hereditary neoplastic syndrome cutaneous mastocytosis

Similar variants

KIT p.Lys642Glu Pathogenic ★★ same residue
KIT p.Lys642Thr Uncertain significance ★ ⚠ same residue
KIT p.Lys642= Likely benign ★ same residue
KIT p.Lys642fs Pathogenic same residue
KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same condition
KIT p.Asp816His Pathogenic ★★ same condition
KIT p.Asp820Tyr Pathogenic ★★ same condition
KIT p.Gln190Ter 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-lys642gln (accessed [today's date]).

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