Is KIT p.Arg888Gln (c.2663G>A) pathogenic?

KIT p.Arg888Gln (c.2663G>A) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-06-01). AlphaMissense: ambiguous (0.4842); Ultra-rare (popmax 0.0116%, nfe); Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Arg888Gln (c.2663G>A)?

KIT p.Arg888Gln (c.2663G>A) is associated with gastrointestinal stromal tumor, piebaldism, testicular germ cell tumor (ClinVar).

How common is KIT p.Arg888Gln (c.2663G>A) in the general population?

KIT p.Arg888Gln (c.2663G>A) is ultra-rare (popmax 0.0116%, nfe) (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.Arg888Gln (c.2663G>A)?

AlphaMissense predicts ambiguous (score 0.4842) — an in-silico prediction, not a clinical call.

KIT p.Arg888Gln

c.2663G>A · rs776681643 · VCV409758

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

ambiguous

0.4842 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0116%, nfe)

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
AlphaMissense	0.4842	ambiguous
REVEL	0.551	indeterminate
SaProt	LLR -10.56	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.5, 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 0.0116% European (non-Finnish) · 137/1,179,992 alleles

Filtering AF 0.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00939%

Overall 0.00905% 146/1,613,960 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0116%	8,613
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Finnishnot grpmax-eligible	0.00312%	32,013
African / African-American	0.00267%	37,455
Admixed American	0.00167%	59,996

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.Arg888Gln
Coding: c.2663G>A
MANE Select: NM_000222
dbSNP: rs776681643
Type: single nucleotide variant
Location: chr4:54736787 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 888: the protein kinase 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

Also linked: piebaldism testicular germ cell tumor hereditary neoplastic syndrome acute myeloid leukemia cutaneous mastocytosis

For Gastrointestinal stromal tumor (Orphanet):

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

Similar variants

KIT p.Arg888Trp Uncertain significance ★★ ⚠ same residue
KIT p.Arg888Leu Uncertain significance ★ ⚠ same residue
KIT p.Arg888= Likely benign ★ same residue
KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same condition
KIT p.Asp816His Pathogenic ★★ same condition
KIT p.Asp820Tyr Pathogenic ★★ same condition
KIT p.Gln190Ter Pathogenic ★★ same condition
KIT p.Leu576Pro 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-arg888gln (accessed [today's date]).

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