Is KIT p.Pro41= (c.123A>T) pathogenic?

KIT p.Pro41= (c.123A>T) is classified Benign/Likely benign in KIT (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-06-02). Rare (popmax 0.613%, afr); Associated with piebaldism.

What condition is associated with KIT p.Pro41= (c.123A>T)?

KIT p.Pro41= (c.123A>T) is associated with piebaldism, mastocytosis, gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Pro41= (c.123A>T) in the general population?

KIT p.Pro41= (c.123A>T) is rare (popmax 0.613%, afr) (gnomAD).

How is Piebaldism inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

KIT p.Pro41=

c.123A>T · rs72549300 · VCV221126

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.613%, afr)

Conditions

piebaldism

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 0.27	GERP -4.5, phastCons 0.53
Overall
CADD	4.662	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.613% African / African-American · 460/75,062 alleles

Filtering AF 0.567% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.548%

Overall 0.0321% 518/1,614,226 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.613%	163
Remaining individualsnot grpmax-eligible	0.048%	2,084
Admixed American	0.0367%	2,728
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.000424%	236,008

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.Pro41=
Coding: c.123A>T
MANE Select: NM_000222
dbSNP: rs72549300
Type: single nucleotide variant
Location: chr4:54695567 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 41: a β-strand; the ig-like c2-type 1 domain

Full KIT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

piebaldism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mastocytosis gastrointestinal stromal tumor hereditary neoplastic syndrome

For Piebaldism (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

KIT p.Pro41Ala Uncertain significance ★★ ⚠ same residue
KIT p.Pro41Leu 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
KIT p.Trp557Arg 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-pro41 (accessed [today's date]).

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