Is KIT p.Asn400Ser (c.1199A>G) pathogenic?

KIT p.Asn400Ser (c.1199A>G) is classified Benign/Likely benign in KIT (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-05-27). AlphaMissense: likely benign (0.0585); Rare (popmax 0.68%, afr); Associated with gastrointestinal stromal tumor.

What condition is associated with KIT p.Asn400Ser (c.1199A>G)?

KIT p.Asn400Ser (c.1199A>G) is associated with gastrointestinal stromal tumor, hereditary neoplastic syndrome (ClinVar).

How common is KIT p.Asn400Ser (c.1199A>G) in the general population?

KIT p.Asn400Ser (c.1199A>G) is rare (popmax 0.68%, afr) (gnomAD).

How is Gastrointestinal stromal tumor inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about KIT p.Asn400Ser (c.1199A>G)?

AlphaMissense predicts likely benign (score 0.0585) — an in-silico prediction, not a clinical call.

KIT p.Asn400Ser

c.1199A>G · rs72549294 · VCV41597

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0585 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.68%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
AlphaMissense	0.0585	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -5.46	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 -1.3	GERP -5.1
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	0.011	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

Grpmax group 0.68% African / African-American · 510/75,018 alleles

Filtering AF 0.631% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.612%

Overall 0.0575% 926/1,611,366 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.68%	147
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0689%	1,451
Admixed American	0.045%	2,223
European (non-Finnish)	0.0279%	3,579
East Asian	0.00892%	11,216
South Asian	0.00769%	13,003
Finnishnot grpmax-eligible	0.00156%	64,032

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.Asn400Ser
Coding: c.1199A>G
MANE Select: NM_000222
dbSNP: rs72549294
Type: single nucleotide variant
Location: chr4:54709507 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 400: a β-strand; the ig-like c2-type 4 domain

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

Disease context

gastrointestinal stromal tumor — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Gastrointestinal stromal tumor (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

KIT p.Asn400Ile Likely benign ★ 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
KIT p.Trp557Arg Pathogenic/Likely pathogenic ★★ same condition
KIT p.Val559Ala 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-asn400ser (accessed [today's date]).

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