Is KIT p.Leu18Phe (c.52C>T) pathogenic?

KIT p.Leu18Phe (c.52C>T) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-05-26). AlphaMissense: likely benign (0.0729); Very rare (popmax 0.00737%, nfe); Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Leu18Phe (c.52C>T)?

KIT p.Leu18Phe (c.52C>T) is associated with gastrointestinal stromal tumor, hereditary neoplastic syndrome (ClinVar).

How common is KIT p.Leu18Phe (c.52C>T) in the general population?

KIT p.Leu18Phe (c.52C>T) is very rare (popmax 0.00737%, 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.Leu18Phe (c.52C>T)?

AlphaMissense predicts likely benign (score 0.0729) — an in-silico prediction, not a clinical call.

KIT p.Leu18Phe

c.52C>T · rs370787811 · VCV409759

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00737%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -8.18	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 -0.033	GERP -0.73, phastCons 0.002
Regional constraint	o/e 1.19	unconstrained · MANE · 38 kb · p 0.24 · regional, not allelic
Overall
CADD	16.66	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 0.00737% European (non-Finnish) · 87/1,179,906 alleles

Filtering AF 0.00605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00565%

Overall 0.0057% 92/1,613,814 alleles · very rare exomes 86/1,461,656 · genomes 6/152,158 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00737%	13,562
Remaining individualsnot grpmax-eligible	0.0048%	20,823
Finnishnot grpmax-eligible	0.00313%	31,997

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.Leu18Phe
Coding: c.52C>T
MANE Select: NM_000222
dbSNP: rs370787811
Type: single nucleotide variant
Location: chr4:54658066 (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.Leu18Arg Uncertain significance ★ ⚠ same residue
KIT p.Leu18Val Uncertain significance ★ ⚠ 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-leu18phe (accessed [today's date]).

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