Is KIT p.Glu839Lys (c.2515G>A) pathogenic?

KIT p.Glu839Lys (c.2515G>A) is classified Pathogenic in KIT (ClinVar, No assertion criteria, 1 submitter; last evaluated 1996-03-01). AlphaMissense: likely pathogenic (0.9981); Absent from gnomAD v4.1; Associated with mastocytosis.

What condition is associated with KIT p.Glu839Lys (c.2515G>A)?

KIT p.Glu839Lys (c.2515G>A) is associated with mastocytosis (ClinVar).

How common is KIT p.Glu839Lys (c.2515G>A) in the general population?

KIT p.Glu839Lys (c.2515G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIT p.Glu839Lys (c.2515G>A)?

AlphaMissense predicts likely pathogenic (score 0.9981) — an in-silico prediction, not a clinical call.

KIT p.Glu839Lys

c.2515G>A · rs121913509 · VCV13862

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9981 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mastocytosis

Computational evidence

Protein change
AlphaMissense	0.9981	likely pathogenic ✓ concordant with ClinVar · top 6% in KIT
REVEL	0.915	moderately pathogenic-leaning
SaProt	LLR -14.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 4,810 bp · p 2.2e-10 · regional, not allelic
Overall
CADD	33.0	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.Glu839Lys
Coding: c.2515G>A
MANE Select: NM_000222
dbSNP: rs121913509
Type: single nucleotide variant
Location: chr4:54736528 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 839: the protein kinase domain; an α-helix; a UniProt-annotated variant site (in mastc; sporadic case; somatic mutation; dominant negative mutation; loss of autophosphorylation)

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

Disease context

mastocytosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KIT p.Ala755Val Uncertain significance ★★ ⚠ same condition
KIT p.Asp765Gly Uncertain significance ★★ ⚠ same condition
KIT p.Asp765Tyr Uncertain significance ★★ ⚠ same condition
KIT p.Asp975His Uncertain significance ★★ ⚠ same condition
KIT p.Gln556Glu Uncertain significance ★★ ⚠ same condition
KIT p.Gln947Ter Uncertain significance ★★ same condition
KIT p.Ile539Thr Uncertain significance ★★ ⚠ same condition
KIT p.Leu71Val Uncertain significance ★★ ⚠ 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-glu839lys (accessed [today's date]).

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