Is SMARCA4 p.Pro232fs (c.695del) pathogenic?

SMARCA4 p.Pro232fs (c.695del) is classified Pathogenic in SMARCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCA4 p.Pro232fs (c.695del)?

SMARCA4 p.Pro232fs (c.695del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SMARCA4 p.Pro232fs (c.695del) in the general population?

SMARCA4 p.Pro232fs (c.695del) is absent from gnomAD (gnomAD).

SMARCA4 p.Pro232fs

c.695del · rs2514004859 · VCV3233142

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

hereditary neoplastic syndrome

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 4 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 10	GERP 2, phastCons 1
Region caveats
Repeat context	tandem	(GGCCCT)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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.Pro232fs
Coding: c.695del
MANE Select: NM_003072
dbSNP: rs2514004859
Type: Deletion
Location: chr19:10986526 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 232: 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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SMARCA4 p.Pro232= Conflicting classifications of pathogenicity ★ 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.Met1000fs Pathogenic ★★ same condition
SMARCA4 p.Phe947fs Pathogenic ★★ same condition
SMARCA4 p.Thr1425fs 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-pro232fs (accessed [today's date]).

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