Is KIT p.Thr84= (c.252G>T) pathogenic?

KIT p.Thr84= (c.252G>T) is classified Benign/Likely benign in KIT (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-06-02). Common (popmax 6.27%, afr) — too common for a highly-penetrant pathogenic allele; Associated with mastocytosis.

What condition is associated with KIT p.Thr84= (c.252G>T)?

KIT p.Thr84= (c.252G>T) is associated with mastocytosis, piebaldism, gastrointestinal stromal tumor (ClinVar).

KIT p.Thr84=

Q: How common is KIT p.Thr84= (c.252G>T) in the general population?

KIT p.Thr84= (c.252G>T) is common (popmax 6.27%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.252G>T · rs56411694 · VCV220764

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 6.27%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

mastocytosis

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 -2.5	GERP -4.5
Overall
CADD	0.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.27% African / African-American · 4,706/75,032 alleles

Filtering AF 6.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.06%

Overall 0.363% 5,859/1,614,180 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.27%	16
Admixed American	0.78%	128
Remaining individualsnot grpmax-eligible	0.555%	180
Middle Eastern	0.478%	209
Ashkenazi Jewishnot grpmax-eligible	0.206%	485
South Asian	0.0231%	4,338
European (non-Finnish)	0.0191%	5,245
East Asian	0.00446%	22,442

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.Thr84=
Coding: c.252G>T
MANE Select: NM_000222
dbSNP: rs56411694
Type: single nucleotide variant
Location: chr4:54695696 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 84: a β-strand; a disulfide bond; the ig-like c2-type 1 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: piebaldism gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

KIT p.Thr84Ser Uncertain significance ★★ ⚠ same residue
KIT p.Thr84Met Benign/Likely benign ★★ same residue
KIT p.Thr84Ala Uncertain significance ★ ⚠ same residue
KIT p.Thr84Lys 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-thr84 (accessed [today's date]).

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