Is SMARCA4 p.Asp697= (c.2091C>T) pathogenic?

SMARCA4 p.Asp697= (c.2091C>T) is classified Likely benign in SMARCA4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Ultra-rare (popmax 0.012%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCA4 p.Asp697= (c.2091C>T)?

SMARCA4 p.Asp697= (c.2091C>T) is associated with hereditary neoplastic syndrome, rhabdoid tumor predisposition syndrome 2 (ClinVar).

How common is SMARCA4 p.Asp697= (c.2091C>T) in the general population?

SMARCA4 p.Asp697= (c.2091C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

SMARCA4 p.Asp697=

c.2091C>T · rs528874054 · VCV415113

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -4.1
Overall
CADD	7.166	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/75,014 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00316% 51/1,613,610 alleles · ultra-rare exomes 43/1,461,328 · genomes 8/152,282 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,335
Remaining individualsnot grpmax-eligible	0.0064%	15,618
Admixed American	0.005%	20,003
East Asian	0.00446%	22,432
European (non-Finnish)	0.0028%	35,747

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SMARCA4
Protein: p.Asp697=
Coding: c.2091C>T
MANE Select: NM_003072
dbSNP: rs528874054
Type: single nucleotide variant
Location: chr19:11007991 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 697: 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

Also linked: rhabdoid tumor predisposition syndrome 2

Similar variants

SMARCA4 p.Asp697Glu Uncertain significance ★ ⚠ 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-asp697 (accessed [today's date]).

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