Is KIT p.Glu69Gln (c.205G>C) pathogenic?

KIT p.Glu69Gln (c.205G>C) is classified Uncertain significance in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-09). AlphaMissense: likely benign (0.1067); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Glu69Gln (c.205G>C)?

KIT p.Glu69Gln (c.205G>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is KIT p.Glu69Gln (c.205G>C) in the general population?

KIT p.Glu69Gln (c.205G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIT p.Glu69Gln (c.205G>C)?

AlphaMissense predicts likely benign (score 0.1067) — an in-silico prediction, not a clinical call.

KIT p.Glu69Gln

c.205G>C · rs2475441379 · VCV2568319

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1067 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1067	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.30	acceptor gain · deltas
Pangolin	Δ0.28	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.2	GERP -1.9, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	20.4	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

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.Glu69Gln
Coding: c.205G>C
MANE Select: NM_000222
dbSNP: rs2475441379
Type: single nucleotide variant
Location: chr4:54695649 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 69: a β-strand; the ig-like c2-type 1 domain

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

Similar variants

KIT p.Glu69= Likely benign ★ same residue
KIT p.Asp820Tyr Pathogenic ★★ same condition
KIT p.Leu576Pro Pathogenic/Likely pathogenic ★★ same condition
KIT p.Trp557Arg Pathogenic/Likely pathogenic ★★ same condition
KIT p.Val559Ala Pathogenic/Likely pathogenic ★★ same condition
KIT c.1232-3T>C Uncertain significance ★★ same condition
KIT c.1647+5C>A Uncertain significance ★★ same condition
KIT c.1647+5C>G 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-glu69gln (accessed [today's date]).

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