Is SMARCA4 p.Pro12fs (c.33_51del) pathogenic?

SMARCA4 p.Pro12fs (c.3351del) is classified Pathogenic in SMARCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-08). No gnomAD frequency available for this variant; Associated with rhabdoid tumor predisposition syndrome 2.

What condition is associated with SMARCA4 p.Pro12fs (c.33_51del)?

SMARCA4 p.Pro12fs (c.33_51del) is associated with rhabdoid tumor predisposition syndrome 2 (ClinVar).

How common is SMARCA4 p.Pro12fs (c.33_51del) in the general population?

SMARCA4 p.Pro12fs (c.33_51del) is no gnomAD frequency available for this variant (gnomAD).

How is Rhabdoid tumor predisposition syndrome inherited?

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

SMARCA4 p.Pro12fs

c.33_51del · rs2513932327 · VCV2843740

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

rhabdoid tumor predisposition syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.3	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Pro12fs
Coding: c.33_51del
MANE Select: NM_003072
dbSNP: rs2513932327
Type: Deletion
Location: chr19:10984183 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 12: the 'necessary for interaction with ss18l1/crest' region; the 'disordered' region

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.Pro12Leu Uncertain significance ★★ same residue
SMARCA4 p.Pro12His Uncertain significance ★ same residue
SMARCA4 p.Pro12= Likely benign ★ same residue
SMARCA4 c.1246-2_1246del Likely pathogenic ★★ same condition
SMARCA4 c.3874delG Pathogenic ★★ same condition
SMARCA4 p.Arg192fs Pathogenic ★★ same condition
SMARCA4 p.Gln194fs Pathogenic ★★ same condition
SMARCA4 p.Leu928fs 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/smarca4-p-pro12fs (accessed [today's date]).

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