Is KIT p.Val530Ile (c.1588G>A) pathogenic?

KIT p.Val530Ile (c.1588G>A) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 13 submitters; last evaluated 2026-05-27). AlphaMissense: likely benign (0.0803); Rare (popmax 0.193%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Val530Ile (c.1588G>A)?

KIT p.Val530Ile (c.1588G>A) is associated with hereditary neoplastic syndrome, mastocytosis, piebaldism (ClinVar).

How common is KIT p.Val530Ile (c.1588G>A) in the general population?

KIT p.Val530Ile (c.1588G>A) is rare (popmax 0.193%, afr) (gnomAD).

What do computational predictors say about KIT p.Val530Ile (c.1588G>A)?

AlphaMissense predicts likely benign (score 0.0803) — an in-silico prediction, not a clinical call.

KIT p.Val530Ile

c.1588G>A · rs72550822 · VCV134621

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 13 submitters

AlphaMissense

likely benign

0.0803 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.193%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0803	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -1.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 277 bp · p 0.96 · regional, not allelic
Overall
CADD	19.83	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 0.193% African / African-American · 145/75,036 alleles

Filtering AF 0.168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.158%

Overall 0.0986% 1,592/1,614,144 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.193%	517
European (non-Finnish)	0.112%	889
Remaining individualsnot grpmax-eligible	0.102%	977
Admixed American	0.0866%	1,154
Middle Eastern	0.0165%	6,062
South Asian	0.0022%	45,542
Finnishnot grpmax-eligible	0.00156%	64,026

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.Val530Ile
Coding: c.1588G>A
MANE Select: NM_000222
dbSNP: rs72550822
Type: single nucleotide variant
Location: chr4:54727265 (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: mastocytosis piebaldism gastrointestinal stromal tumor

Similar variants

KIT p.Val530Leu Uncertain significance ★★ ⚠ same residue
KIT p.Val530Gly 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-val530ile (accessed [today's date]).

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