Is KIT p.Leu702Val (c.2104C>G) pathogenic?

KIT p.Leu702Val (c.2104C>G) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-30). AlphaMissense: likely benign (0.0803); Ultra-rare (popmax 0.015%, amr); Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Leu702Val (c.2104C>G)?

KIT p.Leu702Val (c.2104C>G) is associated with gastrointestinal stromal tumor, testicular cancer, mastocytosis (ClinVar).

How common is KIT p.Leu702Val (c.2104C>G) in the general population?

KIT p.Leu702Val (c.2104C>G) is ultra-rare (popmax 0.015%, amr) (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.Leu702Val (c.2104C>G)?

AlphaMissense predicts likely benign (score 0.0803) — an in-silico prediction, not a clinical call.

KIT p.Leu702Val

c.2104C>G · rs768847037 · VCV409779

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0803 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
AlphaMissense	0.0803	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -6.02	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 4.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 4,114 bp · p 4.1e-05 · regional, not allelic
Overall
CADD	20.2	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 0.015% Admixed American · 9/59,998 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.000958% 14/1,461,358 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,666
South Asian	0.00549%	18,214

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.Leu702Val
Coding: c.2104C>G
MANE Select: NM_000222
dbSNP: rs768847037
Type: single nucleotide variant
Location: chr4:54729448 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 702: 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: testicular cancer mastocytosis piebaldism hereditary neoplastic syndrome acute myeloid leukemia

For Gastrointestinal stromal tumor (Orphanet):

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

Similar variants

KIT p.Leu702Phe Uncertain significance ★★ ⚠ same residue
KIT p.Leu702Pro 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-leu702val (accessed [today's date]).

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