Is KIT p.Phe529= (c.1587C>T) pathogenic?

KIT p.Phe529= (c.1587C>T) is classified Benign/Likely benign in KIT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-06-03). Rare (popmax 0.158%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Phe529= (c.1587C>T)?

KIT p.Phe529= (c.1587C>T) is associated with hereditary neoplastic syndrome, gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Phe529= (c.1587C>T) in the general population?

KIT p.Phe529= (c.1587C>T) is rare (popmax 0.158%, amr) (gnomAD).

KIT p.Phe529=

c.1587C>T · rs148248559 · VCV237247

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.158%, amr)

Conditions

hereditary neoplastic syndrome

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 -0.45	GERP -4.9, phastCons 0.13
Overall
CADD	4.403	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.158% Admixed American · 95/60,018 alleles

Filtering AF 0.133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.00898% 145/1,614,110 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.158%	632
Remaining individualsnot grpmax-eligible	0.0448%	2,233
South Asian	0.00878%	11,384
African / African-American	0.004%	25,006
European (non-Finnish)	0.000932%	107,273

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.Phe529=
Coding: c.1587C>T
MANE Select: NM_000222
dbSNP: rs148248559
Type: single nucleotide variant
Location: chr4:54727264 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB

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.Phe529Ser Uncertain significance ★★ ⚠ same residue
KIT p.Phe529Cys Uncertain significance ★ ⚠ same residue
KIT p.Phe529Leu 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-phe529 (accessed [today's date]).

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