Is KIT p.Ser967Phe (c.2900C>T) pathogenic?

KIT p.Ser967Phe (c.2900C>T) is classified Uncertain significance in KIT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-05). AlphaMissense: likely benign (0.2878); No allele count reported in gnomAD v4.1 (AN 1,614,110); Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Ser967Phe (c.2900C>T)?

KIT p.Ser967Phe (c.2900C>T) is associated with gastrointestinal stromal tumor, hereditary neoplastic syndrome (ClinVar).

How common is KIT p.Ser967Phe (c.2900C>T) in the general population?

KIT p.Ser967Phe (c.2900C>T) is no allele count reported in gnomAD v4.1 (AN 1,614,110) (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.Ser967Phe (c.2900C>T)?

AlphaMissense predicts likely benign (score 0.2878) — an in-silico prediction, not a clinical call.

KIT p.Ser967Phe

c.2900C>T · rs1232060384 · VCV2676220

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2878 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,110)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
AlphaMissense	0.2878	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -9.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,746 bp · p 0.88 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,614,110). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: KIT
Protein: p.Ser967Phe
Coding: c.2900C>T
MANE Select: NM_000222
dbSNP: rs1232060384
Type: single nucleotide variant
Location: chr4:54738526 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB

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.Ser967Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
KIT p.Ser967Pro Uncertain significance ★ ⚠ same residue
KIT p.Ser967= 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-ser967phe (accessed [today's date]).

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