Is KIT p.Phe584Cys (c.1751T>G) pathogenic?

KIT p.Phe584Cys (c.1751T>G) is classified Pathogenic in KIT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2000-11-06). AlphaMissense: likely pathogenic (0.9979); Absent from gnomAD v4.1; Associated with piebaldism.

What condition is associated with KIT p.Phe584Cys (c.1751T>G)?

KIT p.Phe584Cys (c.1751T>G) is associated with piebaldism (ClinVar).

How common is KIT p.Phe584Cys (c.1751T>G) in the general population?

KIT p.Phe584Cys (c.1751T>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.Phe584Cys (c.1751T>G)?

AlphaMissense predicts likely pathogenic (score 0.9979) — an in-silico prediction, not a clinical call.

KIT p.Phe584Cys

c.1751T>G · rs28933371 · VCV13864

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9979 · 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	0.9979	likely pathogenic ✓ concordant with ClinVar · top 7% in KIT
REVEL	0.985	strongly pathogenic-leaning
SaProt	LLR -12.14	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 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.19	constrained · MANE · 374 bp · p 8.6e-07 · regional, not allelic
Overall
CADD	32.0	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.Phe584Cys
Coding: c.1751T>G
MANE Select: NM_000222
dbSNP: rs28933371
Type: single nucleotide variant
Location: chr4:54727519 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 584: a UniProt-annotated variant site (in pbt)

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.Phe584Leu Uncertain significance ★ ⚠ same residue
KIT p.Phe584= Benign/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-phe584cys (accessed [today's date]).

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