Is KIT p.Ile935= (c.2805T>A) pathogenic?

KIT p.Ile935= (c.2805T>A) is classified Benign/Likely benign in KIT (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-06-05). Rare (popmax 0.66%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Ile935= (c.2805T>A)?

KIT p.Ile935= (c.2805T>A) is associated with hereditary neoplastic syndrome, mastocytosis, piebaldism (ClinVar).

How common is KIT p.Ile935= (c.2805T>A) in the general population?

KIT p.Ile935= (c.2805T>A) is rare (popmax 0.66%, mid) (gnomAD).

KIT p.Ile935=

c.2805T>A · rs72549296 · VCV221133

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

rare (popmax 0.66%, mid)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.024, phastCons 1
Overall
CADD	8.468	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.66% Middle Eastern · 40/6,060 alleles

Filtering AF 0.498% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.442%

Overall 0.233% 3,766/1,614,032 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.76%	132
Middle Easterngrpmax	0.66%	152
Remaining individualsnot grpmax-eligible	0.269%	372
European (non-Finnish)	0.253%	395
Admixed American	0.23%	435
South Asian	0.178%	562
African / African-American	0.0453%	2,206
Finnishnot grpmax-eligible	0.00937%	10,672
East Asian	0.00446%	22,427

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.Ile935=
Coding: c.2805T>A
MANE Select: NM_000222
dbSNP: rs72549296
Type: single nucleotide variant
Location: chr4:54738431 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 935: the protein kinase 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: mastocytosis piebaldism gastrointestinal stromal tumor

Similar variants

KIT p.Ile935Thr Uncertain significance ★★ ⚠ same residue
KIT p.Ile935Asn Uncertain significance ★ ⚠ same residue
KIT p.Ile935Phe Uncertain significance ★ ⚠ same residue
KIT p.Ile935Val Conflicting classifications of pathogenicity ★ ⚠ 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

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-ile935 (accessed [today's date]).

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