Is SMARCA4 p.Asp702= (c.2106C>T) pathogenic?

SMARCA4 p.Asp702= (c.2106C>T) is classified Likely benign in SMARCA4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-10). Ultra-rare (popmax 0.0165%, mid); Associated with rhabdoid tumor predisposition syndrome 2.

What condition is associated with SMARCA4 p.Asp702= (c.2106C>T)?

SMARCA4 p.Asp702= (c.2106C>T) is associated with rhabdoid tumor predisposition syndrome 2, hereditary neoplastic syndrome (ClinVar).

How common is SMARCA4 p.Asp702= (c.2106C>T) in the general population?

SMARCA4 p.Asp702= (c.2106C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Rhabdoid tumor predisposition syndrome inherited?

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

SMARCA4 p.Asp702=

c.2106C>T · rs758781256 · VCV706714

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

rhabdoid tumor predisposition syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.34	donor gain · deltas
Constraint at this position
Conservation	phyloP -16	GERP -4.1
Overall
CADD	9.067	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000744% 12/1,613,312 alleles · ultra-rare exomes 12/1,461,074 · genomes 0/152,238 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Admixed American	0.00167%	59,964
Remaining individualsnot grpmax-eligible	0.0016%	62,450
South Asian	0.0011%	91,028
European (non-Finnish)	0.000678%	147,440

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.Asp702=
Coding: c.2106C>T
MANE Select: NM_003072
dbSNP: rs758781256
Type: single nucleotide variant
Location: chr19:11008006 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 702: 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

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

Also linked: hereditary neoplastic syndrome

For Rhabdoid tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

SMARCA4 p.Asp702Tyr 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-asp702 (accessed [today's date]).

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