Is KIT p.Arg830Gln (c.2489G>A) pathogenic?

KIT p.Arg830Gln (c.2489G>A) is classified Uncertain significance in KIT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-20). AlphaMissense: likely pathogenic (0.9747); Very rare (popmax 0.00803%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Arg830Gln (c.2489G>A)?

KIT p.Arg830Gln (c.2489G>A) is associated with hereditary neoplastic syndrome, gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Arg830Gln (c.2489G>A) in the general population?

KIT p.Arg830Gln (c.2489G>A) is very rare (popmax 0.00803%, afr) (gnomAD).

What do computational predictors say about KIT p.Arg830Gln (c.2489G>A)?

AlphaMissense predicts likely pathogenic (score 0.9747) — an in-silico prediction, not a clinical call.

KIT p.Arg830Gln

c.2489G>A · rs772311731 · VCV528546

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9747 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00803%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9747	likely pathogenic
REVEL	0.726	pathogenic-leaning
SaProt	LLR -10.60	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 10	GERP 2.6, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 4,810 bp · p 2.2e-10 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.00803% African / African-American · 6/74,766 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00087% 14/1,608,578 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00803%	12,461
European (non-Finnish)	0.000681%	146,897

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: KIT
Protein: p.Arg830Gln
Coding: c.2489G>A
MANE Select: NM_000222
dbSNP: rs772311731
Type: single nucleotide variant
Location: chr4:54736502 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 830: the protein kinase domain; a β-strand

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastrointestinal stromal tumor

Similar variants

KIT p.Arg830Pro Uncertain significance ★★ ⚠ same residue
KIT p.Arg830Gly Uncertain significance ★ ⚠ same residue
KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same condition
KIT p.Asp820Tyr Pathogenic ★★ same condition
KIT p.Gln190Ter Pathogenic ★★ same condition
KIT p.Leu576Pro Pathogenic/Likely pathogenic ★★ same condition
KIT p.Lys642Glu Pathogenic ★★ same condition
KIT p.Trp557Arg Pathogenic/Likely 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-arg830gln (accessed [today's date]).

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