Is KIT p.Val331= (c.993A>T) pathogenic?

KIT p.Val331= (c.993A>T) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-31). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Val331= (c.993A>T)?

KIT p.Val331= (c.993A>T) is associated with hereditary neoplastic syndrome, gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Val331= (c.993A>T) in the general population?

KIT p.Val331= (c.993A>T) is absent from gnomAD v4.1 (gnomAD).

KIT p.Val331=

c.993A>T · rs1553888778 · VCV1541390

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.4	GERP -4.9
Overall
CADD	2.97	PHRED · no single calibrated threshold — expert panels disagree

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.Val331=
Coding: c.993A>T
MANE Select: NM_000222
dbSNP: rs1553888778
Type: single nucleotide variant
Location: chr4:54707165 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 331: a β-strand; the ig-like c2-type 4 domain

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.Val331Ala Uncertain significance ★★ ⚠ same residue
KIT p.Val331Ile Likely benign ★ ⚠ 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-val331 (accessed [today's date]).

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