Is SMARCA4 p.Lys188Arg (c.563A>G) pathogenic?

SMARCA4 p.Lys188Arg (c.563A>G) is classified Uncertain significance in SMARCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-30). AlphaMissense: ambiguous (0.4415); Absent from gnomAD v4.1; Associated with rhabdoid tumor predisposition syndrome 2.

What condition is associated with SMARCA4 p.Lys188Arg (c.563A>G)?

SMARCA4 p.Lys188Arg (c.563A>G) is associated with rhabdoid tumor predisposition syndrome 2 (ClinVar).

How common is SMARCA4 p.Lys188Arg (c.563A>G) in the general population?

SMARCA4 p.Lys188Arg (c.563A>G) is absent from gnomAD v4.1 (gnomAD).

How is Rhabdoid tumor predisposition syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SMARCA4 p.Lys188Arg (c.563A>G)?

AlphaMissense predicts ambiguous (score 0.4415) — an in-silico prediction, not a clinical call.

SMARCA4 p.Lys188Arg

c.563A>G · rs2086034556 · VCV1040190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4415 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,597,864)

Conditions

rhabdoid tumor predisposition syndrome 2

Computational evidence

Protein change
AlphaMissense	0.4415	ambiguous
REVEL	0.625	indeterminate
SaProt	LLR -10.90	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.18	constrained · MANE · 56 bp · p 8.4e-05 · regional, not allelic
Overall
CADD	25.8	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

No allele count reported in gnomAD v4.1 (AN 1,597,864). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SMARCA4
Protein: p.Lys188Arg
Coding: c.563A>G
MANE Select: NM_003072
dbSNP: rs2086034556
Type: single nucleotide variant
Location: chr19:10986396 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 188: the qlq domain; a modified residue (n6-acetyllysine); the 'necessary for interaction with ss18l1/crest' region; an α-helix

Full SMARCA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

rhabdoid tumor predisposition syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Rhabdoid tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

SMARCA4 p.Lys188= Likely benign ★ same residue
SMARCA4 c.1943+1G>A Likely pathogenic ★★ same condition
SMARCA4 c.2274+1G>T Likely pathogenic ★★ same condition
SMARCA4 c.2438+1G>A Pathogenic/Likely pathogenic ★★ same condition
SMARCA4 c.3216-1G>C Likely pathogenic ★★ same condition
SMARCA4 c.3216-2A>G Likely pathogenic ★★ same condition
SMARCA4 c.3546+1G>A Likely pathogenic ★★ same condition
SMARCA4 c.3774+2T>A 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/smarca4-p-lys188arg (accessed [today's date]).

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