Is KIT p.Leu783= (c.2349C>T) pathogenic?

KIT p.Leu783= (c.2349C>T) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-06-04). Ultra-rare (popmax 0.0505%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Leu783= (c.2349C>T)?

KIT p.Leu783= (c.2349C>T) is associated with hereditary neoplastic syndrome, mastocytosis, piebaldism (ClinVar).

How common is KIT p.Leu783= (c.2349C>T) in the general population?

KIT p.Leu783= (c.2349C>T) is ultra-rare (popmax 0.0505%, sas) (gnomAD).

KIT p.Leu783=

c.2349C>T · rs151046591 · VCV237260

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0505%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.1	GERP -5.1
Overall
CADD	2.145	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0505% South Asian · 46/91,030 alleles

Filtering AF 0.0389% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0348%

Overall 0.0329% 530/1,612,434 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0505%	1,979
European (non-Finnish)	0.0383%	2,610
Remaining individualsnot grpmax-eligible	0.0368%	2,717
African / African-American	0.0107%	9,319
Admixed American	0.00167%	59,866

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.Leu783=
Coding: c.2349C>T
MANE Select: NM_000222
dbSNP: rs151046591
Type: single nucleotide variant
Location: chr4:54731986 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 783: the protein kinase domain; an α-helix

Full KIT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mastocytosis piebaldism gastrointestinal stromal tumor

Similar variants

KIT p.Leu783Val 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
KIT p.Val559Ala 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-leu783 (accessed [today's date]).

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