Is KIT p.Arg804Gln (c.2411G>A) pathogenic?

KIT p.Arg804Gln (c.2411G>A) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-05-29). AlphaMissense: ambiguous (0.4738); Very rare (popmax 0.00223%, eas); Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Arg804Gln (c.2411G>A)?

KIT p.Arg804Gln (c.2411G>A) is associated with gastrointestinal stromal tumor, hereditary neoplastic syndrome (ClinVar).

How common is KIT p.Arg804Gln (c.2411G>A) in the general population?

KIT p.Arg804Gln (c.2411G>A) is very rare (popmax 0.00223%, eas) (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.Arg804Gln (c.2411G>A)?

AlphaMissense predicts ambiguous (score 0.4738) — an in-silico prediction, not a clinical call.

KIT p.Arg804Gln

c.2411G>A · rs777616126 · VCV577278

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4738 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
AlphaMissense	0.4738	ambiguous
REVEL	0.607	indeterminate
SaProt	LLR -10.44	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.62, 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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,810 alleles

Filtering AF 0.000544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000994% 16/1,610,372 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00321%	31,179
East Asiangrpmax	0.00223%	44,810
South Asian	0.0011%	91,004
European (non-Finnish)	0.00102%	98,084

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg804Gln
Coding: c.2411G>A
MANE Select: NM_000222
dbSNP: rs777616126
Type: single nucleotide variant
Location: chr4:54733119 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 804: the protein kinase domain; an α-helix; a UniProt-annotated variant site (in a colorectal adenocarcinoma sample; somatic mutation)

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

Also linked: hereditary neoplastic syndrome

For Gastrointestinal stromal tumor (Orphanet):

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

Similar variants

KIT p.Arg804Leu Uncertain significance ★★ ⚠ same residue
KIT p.Arg804Trp 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
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-arg804gln (accessed [today's date]).

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