Is KIT p.Ser28= (c.84T>C) pathogenic?

KIT p.Ser28= (c.84T>C) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-06-02). Very rare (popmax 0.00636%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Ser28= (c.84T>C)?

KIT p.Ser28= (c.84T>C) is associated with hereditary neoplastic syndrome, gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Ser28= (c.84T>C) in the general population?

KIT p.Ser28= (c.84T>C) is very rare (popmax 0.00636%, nfe) (gnomAD).

KIT p.Ser28=

c.84T>C · rs758868843 · VCV458972

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00636%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 2.2, phastCons 1
Overall
CADD	12.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00636% European (non-Finnish) · 75/1,180,036 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.00465% 75/1,614,094 alleles · very rare

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.Ser28=
Coding: c.84T>C
MANE Select: NM_000222
dbSNP: rs758868843
Type: single nucleotide variant
Location: chr4:54695528 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 28: the ig-like c2-type 1 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: gastrointestinal stromal tumor

Similar variants

KIT p.Ser28Ala Uncertain significance ★★ ⚠ same residue
KIT p.Ser28Pro Uncertain significance ★ ⚠ same residue
KIT p.Ser28Thr 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-ser28 (accessed [today's date]).

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