Is KIT p.Asn326Lys (c.978C>G) pathogenic?

KIT p.Asn326Lys (c.978C>G) is classified Uncertain significance in KIT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-02). AlphaMissense: likely benign (0.1373); Very rare (popmax 0.000348%, nfe); Associated with cutaneous mastocytosis.

What condition is associated with KIT p.Asn326Lys (c.978C>G)?

KIT p.Asn326Lys (c.978C>G) is associated with cutaneous mastocytosis, piebaldism, testicular germ cell tumor (ClinVar).

How common is KIT p.Asn326Lys (c.978C>G) in the general population?

KIT p.Asn326Lys (c.978C>G) is very rare (popmax 0.000348%, nfe) (gnomAD).

What do computational predictors say about KIT p.Asn326Lys (c.978C>G)?

AlphaMissense predicts likely benign (score 0.1373) — an in-silico prediction, not a clinical call.

KIT p.Asn326Lys

c.978C>G · rs148594615 · VCV859867

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1373 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000348%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cutaneous mastocytosis

Computational evidence

Protein change
AlphaMissense	0.1373	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -5.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -4.9
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	0.035	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

Grpmax group 0.000348% European (non-Finnish) · 4/1,150,180 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.00028% 4/1,428,754 alleles · very rare

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.Asn326Lys
Coding: c.978C>G
MANE Select: NM_000222
dbSNP: rs148594615
Type: single nucleotide variant
Location: chr4:54707150 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 326: the ig-like c2-type 4 domain

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

Disease context

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

Also linked: piebaldism testicular germ cell tumor gastrointestinal stromal tumor hereditary neoplastic syndrome acute myeloid leukemia

Similar variants

KIT p.Asn326Ser Uncertain significance ★★ ⚠ same residue
KIT p.Asn326= Conflicting classifications of pathogenicity ★ same residue
KIT p.Asn326Asp Uncertain significance ★ ⚠ same residue
KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same condition
KIT p.Asp816His Pathogenic ★★ same condition
KIT p.Asp820Tyr Pathogenic ★★ same condition
KIT p.Gln190Ter Pathogenic ★★ same condition
KIT p.Leu576Pro 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-asn326lys (accessed [today's date]).

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