Is KIT p.Arg19Ser (c.55C>A) pathogenic?

KIT p.Arg19Ser (c.55C>A) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-21). AlphaMissense: likely benign (0.1449); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Arg19Ser (c.55C>A)?

KIT p.Arg19Ser (c.55C>A) is associated with hereditary neoplastic syndrome, gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Arg19Ser (c.55C>A) in the general population?

KIT p.Arg19Ser (c.55C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIT p.Arg19Ser (c.55C>A)?

AlphaMissense predicts likely benign (score 0.1449) — an in-silico prediction, not a clinical call.

KIT p.Arg19Ser

c.55C>A · rs1490714621 · VCV1487867

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1449 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1449	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -5.20	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 -0.19	GERP -3.5
Regional constraint	o/e 1.19	unconstrained · MANE · 38 kb · p 0.24 · regional, not allelic
Overall
CADD	15.94	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KIT
Protein: p.Arg19Ser
Coding: c.55C>A
MANE Select: NM_000222
dbSNP: rs1490714621
Type: single nucleotide variant
Location: chr4:54658069 (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: gastrointestinal stromal tumor

Similar variants

KIT p.Arg19His Uncertain significance ★★ ⚠ same residue
KIT p.Arg19Cys Uncertain significance ★ ⚠ same residue
KIT p.Arg19Leu Uncertain significance ★ ⚠ same residue
KIT p.Arg19= Likely benign ★ same residue
KIT p.Arg19Gln Uncertain significance ★ 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-arg19ser (accessed [today's date]).

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