Is KIT p.Ser891Ile (c.2672G>T) pathogenic?

KIT p.Ser891Ile (c.2672G>T) is classified Uncertain significance in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-25). AlphaMissense: ambiguous (0.3572); Absent from gnomAD v4.1; Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Ser891Ile (c.2672G>T)?

KIT p.Ser891Ile (c.2672G>T) is associated with gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Ser891Ile (c.2672G>T) in the general population?

KIT p.Ser891Ile (c.2672G>T) 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.Ser891Ile (c.2672G>T)?

AlphaMissense predicts ambiguous (score 0.3572) — an in-silico prediction, not a clinical call.

KIT p.Ser891Ile

c.2672G>T · rs1560424985 · VCV578876

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3572 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
AlphaMissense	0.3572	ambiguous
REVEL	0.525	indeterminate
SaProt	LLR -6.39	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 4,810 bp · p 2.2e-10 · regional, not allelic
Overall
CADD	28.4	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.Ser891Ile
Coding: c.2672G>T
MANE Select: NM_000222
dbSNP: rs1560424985
Type: single nucleotide variant
Location: chr4:54736796 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 891: the protein kinase domain; an α-helix; a modified residue (phosphoserine)

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.Ser891Gly Uncertain significance ★★ ⚠ same residue
KIT p.Ser891Arg Uncertain significance ★ ⚠ same residue
KIT p.Ser891= Likely benign ★ 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

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-ser891ile (accessed [today's date]).

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