Is KIT p.Ile808Met (c.2424T>G) pathogenic?

KIT p.Ile808Met (c.2424T>G) is classified Pathogenic in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-18). AlphaMissense: likely pathogenic (0.9742); Absent from gnomAD v4.1; Associated with piebaldism.

What condition is associated with KIT p.Ile808Met (c.2424T>G)?

KIT p.Ile808Met (c.2424T>G) is associated with piebaldism (ClinVar).

How common is KIT p.Ile808Met (c.2424T>G) in the general population?

KIT p.Ile808Met (c.2424T>G) is absent from gnomAD v4.1 (gnomAD).

How is Piebaldism inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about KIT p.Ile808Met (c.2424T>G)?

AlphaMissense predicts likely pathogenic (score 0.9742) — an in-silico prediction, not a clinical call.

KIT p.Ile808Met

c.2424T>G · VCV4538531

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9742 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

piebaldism

Computational evidence

Protein change
AlphaMissense	0.9742	likely pathogenic ✓ concordant with ClinVar
REVEL	0.849	moderately pathogenic-leaning
SaProt	LLR -14.73	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 0.66	GERP 0.23, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 4,810 bp · p 2.2e-10 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

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.Ile808Met
Coding: c.2424T>G
MANE Select: NM_000222
Type: single nucleotide variant
Location: chr4:54733132 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 808: the protein kinase domain; a β-strand

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

Disease context

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

For Piebaldism (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

KIT p.Ile808Phe Likely pathogenic ★ same residue
KIT p.Ile808= Likely benign ★ same residue
KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same condition
KIT c.2141+3A>G Uncertain significance ★★ same condition
KIT c.67+5G>T Uncertain significance ★★ same condition
KIT p.Arg634Trp Uncertain significance ★★ ⚠ same condition
KIT p.Asn326Lys Uncertain significance ★★ ⚠ same condition
KIT p.Asp765Gly 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-p-ile808met (accessed [today's date]).

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