Is KIT p.Pro627= (c.1881G>A) pathogenic?

KIT p.Pro627= (c.1881G>A) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-06-04). Very rare (popmax 0.000932%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Pro627= (c.1881G>A)?

KIT p.Pro627= (c.1881G>A) is associated with hereditary neoplastic syndrome, gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Pro627= (c.1881G>A) in the general population?

KIT p.Pro627= (c.1881G>A) is very rare (popmax 0.000932%, nfe) (gnomAD).

KIT p.Pro627=

c.1881G>A · rs971280269 · VCV528641

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.68	GERP -3.4, phastCons 0.94
Overall
CADD	15.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,768 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000744% 12/1,613,664 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)grpmax	0.000932%	107,252

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro627=
Coding: c.1881G>A
MANE Select: NM_000222
dbSNP: rs971280269
Type: single nucleotide variant
Location: chr4:54728012 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 627: the protein kinase domain; an α-helix

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.Pro627Ala Uncertain significance ★★ ⚠ same residue
KIT p.Pro627Leu Uncertain significance ★★ ⚠ same residue
KIT p.Pro627Ser Uncertain significance ★★ ⚠ same residue
KIT p.Pro627Thr 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-pro627 (accessed [today's date]).

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