Is KIT p.Ala533Asp (c.1598C>A) pathogenic?

KIT p.Ala533Asp (c.1598C>A) is classified Pathogenic in KIT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-06-25). AlphaMissense: likely pathogenic (0.9728); Absent from gnomAD v4.1; Associated with cutaneous mastocytosis.

What condition is associated with KIT p.Ala533Asp (c.1598C>A)?

KIT p.Ala533Asp (c.1598C>A) is associated with cutaneous mastocytosis (ClinVar).

How common is KIT p.Ala533Asp (c.1598C>A) in the general population?

KIT p.Ala533Asp (c.1598C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIT p.Ala533Asp (c.1598C>A)?

AlphaMissense predicts likely pathogenic (score 0.9728) — an in-silico prediction, not a clinical call.

KIT p.Ala533Asp

c.1598C>A · rs753212327 · VCV545643

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9728 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cutaneous mastocytosis

Computational evidence

Protein change
AlphaMissense	0.9728	likely pathogenic ✓ concordant with ClinVar
REVEL	0.669	pathogenic-leaning
SaProt	LLR -10.40	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 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 277 bp · p 0.96 · regional, not allelic
Overall
CADD	24.5	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.Ala533Asp
Coding: c.1598C>A
MANE Select: NM_000222
dbSNP: rs753212327
Type: single nucleotide variant
Location: chr4:54727275 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 533: a UniProt-annotated variant site (in mastc; uncertain significance)

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

Disease context

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

Similar variants

KIT p.Ala533Thr Uncertain significance ★★ ⚠ same residue
KIT p.Ala533Val Uncertain significance ★★ ⚠ same residue
KIT p.Ala533Gly Uncertain significance ★ ⚠ same residue
KIT p.Ala533= Likely benign ★ same residue
KIT p.Val559Ala Pathogenic/Likely pathogenic ★★ 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

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-ala533asp (accessed [today's date]).

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