Is KIT p.Asp765Tyr (c.2293G>T) pathogenic?

KIT p.Asp765Tyr (c.2293G>T) is classified Uncertain significance in KIT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). AlphaMissense: likely pathogenic (0.5644); Ultra-rare (popmax 0.01%, amr); Associated with KIT-related disorder.

What condition is associated with KIT p.Asp765Tyr (c.2293G>T)?

KIT p.Asp765Tyr (c.2293G>T) is associated with KIT-related disorder, mastocytosis, piebaldism (ClinVar).

How common is KIT p.Asp765Tyr (c.2293G>T) in the general population?

KIT p.Asp765Tyr (c.2293G>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about KIT p.Asp765Tyr (c.2293G>T)?

AlphaMissense predicts likely pathogenic (score 0.5644) — an in-silico prediction, not a clinical call.

KIT p.Asp765Tyr

c.2293G>T · rs760112920 · VCV458915

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.5644 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

KIT-related disorder

Computational evidence

Protein change
AlphaMissense	0.5644	likely pathogenic
REVEL	0.701	pathogenic-leaning
SaProt	LLR -8.15	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.6, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 4,114 bp · p 4.1e-05 · regional, not allelic
Overall
CADD	24.9	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 0.01% Admixed American · 6/59,958 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00062% 10/1,613,536 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,993
Remaining individualsnot grpmax-eligible	0.0064%	15,620

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.Asp765Tyr
Coding: c.2293G>T
MANE Select: NM_000222
dbSNP: rs760112920
Type: single nucleotide variant
Location: chr4:54731930 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 765: the protein kinase domain

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

Disease context

KIT-related disorder

Also linked: mastocytosis piebaldism gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

KIT p.Asp765Glu Uncertain significance ★★ ⚠ same residue
KIT p.Asp765Gly Uncertain significance ★★ ⚠ same residue
KIT p.Asp765= 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-asp765tyr (accessed [today's date]).

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