Is KIT p.Arg686= (c.2058T>G) pathogenic?

KIT p.Arg686= (c.2058T>G) is classified Likely benign in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-15). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Arg686= (c.2058T>G)?

KIT p.Arg686= (c.2058T>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is KIT p.Arg686= (c.2058T>G) in the general population?

KIT p.Arg686= (c.2058T>G) is absent from gnomAD v4.1 (gnomAD).

KIT p.Arg686=

c.2058T>G · VCV4043766

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor loss, 25 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.33	GERP -5.1, phastCons 0.34
Overall
CADD	8.384	PHRED · no single calibrated threshold — expert panels disagree

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.Arg686=
Coding: c.2058T>G
MANE Select: NM_000222
Type: single nucleotide variant
Location: chr4:54729402 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 686: 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

Similar variants

KIT p.Arg686Leu Uncertain significance ★★ ⚠ same residue
KIT p.Arg686Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
KIT p.Arg686His Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg686 (accessed [today's date]).

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