Is KIT p.Val560Asp (c.1679T>A) pathogenic?

KIT p.Val560Asp (c.1679T>A) is classified Likely pathogenic in KIT (ClinVar, Single submitter, 2 submitters; last evaluated 2024-02-23). AlphaMissense: likely pathogenic (0.9953); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Val560Asp (c.1679T>A)?

KIT p.Val560Asp (c.1679T>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is KIT p.Val560Asp (c.1679T>A) in the general population?

KIT p.Val560Asp (c.1679T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIT p.Val560Asp (c.1679T>A)?

AlphaMissense predicts likely pathogenic (score 0.9953) — an in-silico prediction, not a clinical call.

KIT p.Val560Asp

c.1679T>A · rs121913521 · VCV375914

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9953 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9953	likely pathogenic ✓ concordant with ClinVar · top 9% in KIT
REVEL	0.823	moderately pathogenic-leaning
SaProt	LLR -14.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.45 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 277 bp · p 0.96 · regional, not allelic
Overall
CADD	29.7	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.

Cancer therapy — CIViC

Disease	Therapies	Level	Significance
Gastrointestinal Stromal Tumor	Imatinib	D	Sensitivity/Response
Cancer	Sunitinib	D	Resistance
Gastrointestinal Stromal Tumor	Sunitinib	C	Resistance
Gastrointestinal Stromal Tumor	Sunitinib	C	Sensitivity/Response
Gastrointestinal Stromal Tumor	Sunitinib	C	Sensitivity/Response
Gastrointestinal Stromal Tumor	Ponatinib,Sunitinib,Imatinib,Regorafenib	D	Sensitivity/Response
Cancer	Imatinib Mesylate	D	Sensitivity/Response

Variant & gene context

Gene: KIT
Protein: p.Val560Asp
Coding: c.1679T>A
MANE Select: NM_000222
dbSNP: rs121913521
Type: single nucleotide variant
Location: chr4:54727447 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 560: a β-strand; a UniProt-annotated variant site (in gist; somatic mutation)

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.Val560Ala Uncertain significance ★★ ⚠ same residue
KIT p.Val560Ile Uncertain significance ★ ⚠ same residue
KIT p.Val560Phe Uncertain significance ★ ⚠ 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-val560asp (accessed [today's date]).

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