Is KIT p.Asp140Glu (c.420C>A) pathogenic?

KIT p.Asp140Glu (c.420C>A) is classified Uncertain significance in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-29). AlphaMissense: ambiguous (0.5177); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Asp140Glu (c.420C>A)?

KIT p.Asp140Glu (c.420C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is KIT p.Asp140Glu (c.420C>A) in the general population?

KIT p.Asp140Glu (c.420C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIT p.Asp140Glu (c.420C>A)?

AlphaMissense predicts ambiguous (score 0.5177) — an in-silico prediction, not a clinical call.

KIT p.Asp140Glu

c.420C>A · rs778793243 · VCV1738718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5177 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5177	ambiguous
REVEL	0.414	indeterminate
SaProt	LLR -10.11	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	20.8	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

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.Asp140Glu
Coding: c.420C>A
MANE Select: NM_000222
dbSNP: rs778793243
Type: single nucleotide variant
Location: chr4:54698366 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 140: the ig-like c2-type 2 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

Similar variants

KIT p.Asp140Asn Uncertain significance ★ ⚠ same residue
KIT p.Asp140Tyr Uncertain significance ★ ⚠ same residue
KIT p.Asp820Tyr Pathogenic ★★ same condition
KIT p.Leu576Pro Pathogenic/Likely pathogenic ★★ same condition
KIT p.Trp557Arg Pathogenic/Likely pathogenic ★★ same condition
KIT p.Val559Ala Pathogenic/Likely pathogenic ★★ same condition
KIT c.1232-3T>C Uncertain significance ★★ same condition
KIT c.1647+5C>A Uncertain significance ★★ 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-asp140glu (accessed [today's date]).

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