Is KIT p.Arg804Trp (c.2410C>T) pathogenic?

KIT p.Arg804Trp (c.2410C>T) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-05-29). AlphaMissense: likely pathogenic (0.8545); Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Arg804Trp (c.2410C>T)?

KIT p.Arg804Trp (c.2410C>T) is associated with hereditary neoplastic syndrome, gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Arg804Trp (c.2410C>T) in the general population?

KIT p.Arg804Trp (c.2410C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about KIT p.Arg804Trp (c.2410C>T)?

AlphaMissense predicts likely pathogenic (score 0.8545) — an in-silico prediction, not a clinical call.

KIT p.Arg804Trp

c.2410C>T · rs145602440 · VCV458919

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8545 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.8545	likely pathogenic
REVEL	0.641	indeterminate
SaProt	LLR -13.05	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, 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

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 · 1/44,814 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000261%

Overall 0.000745% 12/1,610,962 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,814
South Asian	0.0022%	45,502
European (non-Finnish)	0.000764%	130,820

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.Arg804Trp
Coding: c.2410C>T
MANE Select: NM_000222
dbSNP: rs145602440
Type: single nucleotide variant
Location: chr4:54733118 (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

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

Also linked: gastrointestinal stromal tumor

Similar variants

KIT p.Arg804Leu Uncertain significance ★★ ⚠ same residue
KIT p.Arg804Gln 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-arg804trp (accessed [today's date]).

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