Is KIT p.Lys193Arg (c.578A>G) pathogenic?

KIT p.Lys193Arg (c.578A>G) is classified Likely benign in KIT (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.0754); Absent from gnomAD v4.1; Associated with EBV-positive nodal T- and NK-cell lymphoma.

What condition is associated with KIT p.Lys193Arg (c.578A>G)?

KIT p.Lys193Arg (c.578A>G) is associated with EBV-positive nodal T- and NK-cell lymphoma (ClinVar).

How common is KIT p.Lys193Arg (c.578A>G) in the general population?

KIT p.Lys193Arg (c.578A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIT p.Lys193Arg (c.578A>G)?

AlphaMissense predicts likely benign (score 0.0754) — an in-silico prediction, not a clinical call.

KIT p.Lys193Arg

c.578A>G · rs2109674531 · VCV2681353

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0754 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EBV-positive nodal T- and NK-cell lymphoma

Computational evidence

Protein change
AlphaMissense	0.0754	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -7.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.91	donor gain · deltas
Pangolin	Δ0.76	gain · loss 0.47 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.51	GERP -4.2
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	17.44	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.Lys193Arg
Coding: c.578A>G
MANE Select: NM_000222
dbSNP: rs2109674531
Type: single nucleotide variant
Location: chr4:54698524 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 193: the ig-like c2-type 2 domain

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

Disease context

EBV-positive nodal T- and NK-cell lymphoma

Similar variants

KIT p.Lys193Asn Uncertain significance ★ ⚠ same residue
KIT p.Lys193Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
KIT p.Lys193Glu Uncertain significance ★ ⚠ same residue
KIT p.Gln190Ter Pathogenic ★★ same condition
KIT p.Leu576Pro Pathogenic/Likely pathogenic ★★ same condition
KIT p.Ala755Val Uncertain significance ★★ ⚠ same condition
KIT p.Asp765Tyr Uncertain significance ★★ ⚠ same condition
KIT p.Tyr936His 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-lys193arg (accessed [today's date]).

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