Is KIT p.Asn326= (c.978C>T) pathogenic?

KIT p.Asn326= (c.978C>T) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-06-03). Ultra-rare (popmax 0.0157%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Asn326= (c.978C>T)?

KIT p.Asn326= (c.978C>T) is associated with hereditary neoplastic syndrome, mastocytosis, piebaldism (ClinVar).

How common is KIT p.Asn326= (c.978C>T) in the general population?

KIT p.Asn326= (c.978C>T) is ultra-rare (popmax 0.0157%, eas) (gnomAD).

KIT p.Asn326=

c.978C>T · rs148594615 · VCV458979

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -4.9
Overall
CADD	0.355	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0157% East Asian · 7/44,672 alleles

Filtering AF 0.0108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0102%

Overall 0.0106% 168/1,580,842 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0157%	6,382
European (non-Finnish)	0.0125%	7,987
African / African-American	0.0108%	9,275
Remaining individualsnot grpmax-eligible	0.00652%	15,333
Admixed American	0.00501%	19,967
South Asian	0.00222%	45,145

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.Asn326=
Coding: c.978C>T
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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mastocytosis piebaldism gastrointestinal stromal tumor

Similar variants

KIT p.Asn326Lys Uncertain significance ★★ ⚠ same residue
KIT p.Asn326Ser Uncertain significance ★★ ⚠ same residue
KIT p.Asn326Asp Uncertain significance ★ ⚠ same residue
KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same condition
KIT p.Asp820Tyr Pathogenic ★★ same condition
KIT p.Gln190Ter Pathogenic ★★ same condition
KIT p.Leu576Pro Pathogenic/Likely pathogenic ★★ same condition
KIT p.Lys642Glu 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-asn326 (accessed [today's date]).

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