Is KIT p.Gly565Val (c.1694G>T) pathogenic?

KIT p.Gly565Val (c.1694G>T) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-05-27). AlphaMissense: likely pathogenic (0.9263); Very rare (popmax 0.00161%, nfe); Associated with mastocytosis.

What condition is associated with KIT p.Gly565Val (c.1694G>T)?

KIT p.Gly565Val (c.1694G>T) is associated with mastocytosis, piebaldism, gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Gly565Val (c.1694G>T) in the general population?

KIT p.Gly565Val (c.1694G>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about KIT p.Gly565Val (c.1694G>T)?

AlphaMissense predicts likely pathogenic (score 0.9263) — an in-silico prediction, not a clinical call.

KIT p.Gly565Val

c.1694G>T · rs200945282 · VCV41600

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely pathogenic

0.9263 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mastocytosis

Computational evidence

Protein change
AlphaMissense	0.9263	likely pathogenic
REVEL	0.812	moderately pathogenic-leaning
SaProt	LLR -9.76	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	loss · gain 0.05 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 277 bp · p 0.96 · regional, not allelic
Overall
CADD	33.0	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 0.00161% European (non-Finnish) · 19/1,179,828 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00837% 135/1,613,736 alleles · very rare exomes 122/1,461,634 · genomes 13/152,102 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.358%	279
Remaining individualsnot grpmax-eligible	0.016%	6,247
European (non-Finnish)grpmax	0.00161%	62,096

Ashkenazi Jewish 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.Gly565Val
Coding: c.1694G>T
MANE Select: NM_000222
dbSNP: rs200945282
Type: single nucleotide variant
Location: chr4:54727462 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 565: a β-strand

Full KIT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mastocytosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: piebaldism gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

KIT p.Gly565Arg Uncertain significance ★★ ⚠ same residue
KIT p.Gly565Glu Uncertain significance ★ ⚠ same residue
KIT p.Gly565= 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

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-gly565val (accessed [today's date]).

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