Is KIT p.Ala482Pro (c.1444G>C) pathogenic?

KIT p.Ala482Pro (c.1444G>C) is classified Uncertain significance in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-11). AlphaMissense: likely benign (0.156); Absent from gnomAD v4.1; Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Ala482Pro (c.1444G>C)?

KIT p.Ala482Pro (c.1444G>C) is associated with gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Ala482Pro (c.1444G>C) in the general population?

KIT p.Ala482Pro (c.1444G>C) is absent from gnomAD v4.1 (gnomAD).

How is Gastrointestinal stromal tumor inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about KIT p.Ala482Pro (c.1444G>C)?

AlphaMissense predicts likely benign (score 0.156) — an in-silico prediction, not a clinical call.

KIT p.Ala482Pro

c.1444G>C · rs1060502569 · VCV2108937

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.156 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
AlphaMissense	0.156	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -11.39	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.31	GERP -2.5
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	14.28	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.Ala482Pro
Coding: c.1444G>C
MANE Select: NM_000222
dbSNP: rs1060502569
Type: single nucleotide variant
Location: chr4:54725954 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 482: an α-helix; the ig-like c2-type 5 domain

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

Disease context

gastrointestinal stromal tumor — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Gastrointestinal stromal tumor (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

KIT p.Ala482Glu Uncertain significance ★★ ⚠ same residue
KIT p.Ala482Ser Uncertain significance ★★ ⚠ same residue
KIT p.Ala482Val Uncertain significance ★★ ⚠ same residue
KIT p.Ala482= Likely benign ★★ same residue
KIT p.Ala482Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
KIT p.Ala621Thr Pathogenic/Likely 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-ala482pro (accessed [today's date]).

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