Is SMARCA4 p.Pro693fs (c.2078del) pathogenic?

SMARCA4 p.Pro693fs (c.2078del) is classified Pathogenic in SMARCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-05). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCA4 p.Pro693fs (c.2078del)?

SMARCA4 p.Pro693fs (c.2078del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SMARCA4 p.Pro693fs (c.2078del) in the general population?

SMARCA4 p.Pro693fs (c.2078del) is no gnomAD frequency available for this variant (gnomAD).

SMARCA4 p.Pro693fs

c.2078del · rs2514565960 · VCV3233086

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 14 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.5	GERP -4.1

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.Pro693fs
Coding: c.2078del
MANE Select: NM_003072
dbSNP: rs2514565960
Type: Deletion
Location: chr19:11007977 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 693: the 'disordered' region; the 'rna-binding region which is sufficient for binding to lncrna evf2' 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.Pro693Arg Uncertain significance ★★ ⚠ same residue
SMARCA4 p.Pro693= Likely benign ★★ same residue
SMARCA4 p.Pro693Leu Uncertain significance ★ ⚠ 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

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-pro693fs (accessed [today's date]).

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