Is KIT p.Pro949= (c.2847C>T) pathogenic?

KIT p.Pro949= (c.2847C>T) is classified Benign in KIT (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-06-05). Common (popmax 5.55%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Pro949= (c.2847C>T)?

KIT p.Pro949= (c.2847C>T) is associated with hereditary neoplastic syndrome, mastocytosis, piebaldism (ClinVar).

KIT p.Pro949=

Q: How common is KIT p.Pro949= (c.2847C>T) in the general population?

KIT p.Pro949= (c.2847C>T) is common (popmax 5.55%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2847C>T · rs56288823 · VCV348955

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 5.55%, afr) — too common for a highly-penetrant pathogenic allele

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 -9	GERP -3
Overall
CADD	1.033	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.55% African / African-American · 4,163/74,988 alleles

Filtering AF 5.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.35%

Overall 0.341% 5,511/1,614,022 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.55%	18
Admixed American	0.563%	178
Middle Eastern	0.528%	189
Remaining individualsnot grpmax-eligible	0.469%	213
European (non-Finnish)	0.0558%	1,793
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,974
South Asian	0.011%	9,108
East Asian	0.00223%	44,860
Finnishnot grpmax-eligible	0.00156%	64,022

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.Pro949=
Coding: c.2847C>T
MANE Select: NM_000222
dbSNP: rs56288823
Type: single nucleotide variant
Location: chr4:54738473 (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: mastocytosis piebaldism gastrointestinal stromal tumor

Similar variants

KIT p.Pro949Thr Uncertain significance ★★ ⚠ same residue
KIT p.Pro949His Conflicting classifications of pathogenicity ★ ⚠ same residue
KIT p.Pro949Leu Uncertain significance ★ ⚠ same residue
KIT p.Pro949Ser 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-pro949 (accessed [today's date]).

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