Is KIT p.Thr304Ala (c.910A>G) pathogenic?

KIT p.Thr304Ala (c.910A>G) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.0927); Rare (popmax 0.473%, eas); Associated with mastocytosis.

What condition is associated with KIT p.Thr304Ala (c.910A>G)?

KIT p.Thr304Ala (c.910A>G) is associated with mastocytosis, ovarian cancer, piebaldism (ClinVar).

How common is KIT p.Thr304Ala (c.910A>G) in the general population?

KIT p.Thr304Ala (c.910A>G) is rare (popmax 0.473%, eas) (gnomAD).

What do computational predictors say about KIT p.Thr304Ala (c.910A>G)?

AlphaMissense predicts likely benign (score 0.0927) — an in-silico prediction, not a clinical call.

KIT p.Thr304Ala

c.910A>G · rs202052259 · VCV41606

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0927 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.473%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

mastocytosis

Computational evidence

Protein change
AlphaMissense	0.0927	likely benign
REVEL	0.526	indeterminate
SaProt	LLR -10.09	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	21.4	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 0.473% East Asian · 212/44,862 alleles

Filtering AF 0.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.4%

Overall 0.0136% 219/1,613,514 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.473%	212
Remaining individualsnot grpmax-eligible	0.0048%	20,828
Admixed American	0.00333%	30,015
African / African-American	0.00133%	75,040
European (non-Finnish)	8.48e-05%	1,179,427

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.Thr304Ala
Coding: c.910A>G
MANE Select: NM_000222
dbSNP: rs202052259
Type: single nucleotide variant
Location: chr4:54703877 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 304: a β-strand; the ig-like c2-type 3 domain

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

Disease context

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

Also linked: ovarian cancer piebaldism gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

KIT p.Thr304= Conflicting classifications of pathogenicity ★ 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-thr304ala (accessed [today's date]).

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