Is KIT p.Pro36Ser (c.106C>T) pathogenic?

KIT p.Pro36Ser (c.106C>T) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.0891); Ultra-rare (popmax 0.0173%, afr); Associated with KIT-related disorder.

What condition is associated with KIT p.Pro36Ser (c.106C>T)?

KIT p.Pro36Ser (c.106C>T) is associated with KIT-related disorder, gastrointestinal stromal tumor, hereditary neoplastic syndrome (ClinVar).

How common is KIT p.Pro36Ser (c.106C>T) in the general population?

KIT p.Pro36Ser (c.106C>T) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

What do computational predictors say about KIT p.Pro36Ser (c.106C>T)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

KIT p.Pro36Ser

c.106C>T · rs781633384 · VCV528585

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

KIT-related disorder

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -9.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.73	GERP -1.6, phastCons 0.19
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	10.36	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% African / African-American · 13/74,928 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.000929% 15/1,614,066 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0173%	5,764
European (non-Finnish)	0.000169%	590,019

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.Pro36Ser
Coding: c.106C>T
MANE Select: NM_000222
dbSNP: rs781633384
Type: single nucleotide variant
Location: chr4:54695550 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 36: the ig-like c2-type 1 domain

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

Disease context

KIT-related disorder

Also linked: gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

KIT p.Pro36Ala Uncertain significance ★★ ⚠ same residue
KIT p.Pro36Thr Uncertain significance ★★ ⚠ same residue
KIT p.Pro36= Likely benign ★★ same residue
KIT p.Pro36Leu 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-pro36ser (accessed [today's date]).

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