Is KIT p.Ala784Thr (c.2350G>A) pathogenic?

KIT p.Ala784Thr (c.2350G>A) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-03-20). AlphaMissense: likely benign (0.2116); Very rare (popmax 0.00268%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Ala784Thr (c.2350G>A)?

KIT p.Ala784Thr (c.2350G>A) is associated with hereditary neoplastic syndrome, piebaldism, gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Ala784Thr (c.2350G>A) in the general population?

KIT p.Ala784Thr (c.2350G>A) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about KIT p.Ala784Thr (c.2350G>A)?

AlphaMissense predicts likely benign (score 0.2116) — an in-silico prediction, not a clinical call.

KIT p.Ala784Thr

c.2350G>A · rs1309976246 · VCV458917

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2116 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2116	likely benign
REVEL	0.446	indeterminate
SaProt	LLR -7.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 4,114 bp · p 4.1e-05 · regional, not allelic
Overall
CADD	26.1	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 0.00268% African / African-American · 2/74,552 alleles

Filtering AF 0.000445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000558% 9/1,612,376 alleles · very rare exomes 8/1,461,280 · genomes 1/151,096 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,276
East Asian	0.00223%	44,828
South Asian	0.0022%	45,514
European (non-Finnish)	0.000339%	294,861

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.Ala784Thr
Coding: c.2350G>A
MANE Select: NM_000222
dbSNP: rs1309976246
Type: single nucleotide variant
Location: chr4:54731987 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 784: the protein kinase domain; an α-helix

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: piebaldism gastrointestinal stromal tumor

Similar variants

KIT p.Ala784= Benign/Likely benign ★★ same residue
KIT p.Ala784Asp Uncertain significance ★ ⚠ same residue
KIT p.Ala784Gly Uncertain significance ★ ⚠ same residue
KIT p.Ala784Ser 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

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-ala784thr (accessed [today's date]).

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