Is KIT p.Pro155Ser (c.463C>T) pathogenic?

KIT p.Pro155Ser (c.463C>T) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-05-26). AlphaMissense: likely benign (0.0866); Very rare (popmax 0.00797%, nfe); Associated with KIT-related disorder.

What condition is associated with KIT p.Pro155Ser (c.463C>T)?

KIT p.Pro155Ser (c.463C>T) is associated with KIT-related disorder, gastrointestinal stromal tumor, hereditary neoplastic syndrome (ClinVar).

How common is KIT p.Pro155Ser (c.463C>T) in the general population?

KIT p.Pro155Ser (c.463C>T) is very rare (popmax 0.00797%, nfe) (gnomAD).

What do computational predictors say about KIT p.Pro155Ser (c.463C>T)?

AlphaMissense predicts likely benign (score 0.0866) — an in-silico prediction, not a clinical call.

KIT p.Pro155Ser

c.463C>T · rs777031731 · VCV237276

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0866 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00797%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

KIT-related disorder

Computational evidence

Protein change
AlphaMissense	0.0866	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -5.72	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 0.87	GERP -4.8, phastCons 0.27
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	13.62	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 0.00797% European (non-Finnish) · 94/1,180,032 alleles

Filtering AF 0.00664% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00616%

Overall 0.00651% 105/1,614,038 alleles · very rare exomes 101/1,461,868 · genomes 4/152,170 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.016%	6,249
European (non-Finnish)grpmax	0.00797%	12,554
African / African-American	0.00133%	74,926

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.Pro155Ser
Coding: c.463C>T
MANE Select: NM_000222
dbSNP: rs777031731
Type: single nucleotide variant
Location: chr4:54698409 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 155: an α-helix; the ig-like c2-type 2 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.Pro155Ala Uncertain significance ★★ ⚠ same residue
KIT p.Pro155Arg Uncertain significance ★ ⚠ same residue
KIT p.Pro155Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
KIT p.Pro155Thr Uncertain significance ★ ⚠ same residue
KIT p.Pro155= Likely benign ★ same residue
KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same condition
KIT p.Asp820Tyr Pathogenic ★★ same condition
KIT p.Gln190Ter 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-pro155ser (accessed [today's date]).

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