Is SMARCA4 p.Asp86= (c.258C>T) pathogenic?

SMARCA4 p.Asp86= (c.258C>T) is classified Benign/Likely benign in SMARCA4 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-04-01). Rare (popmax 0.487%, afr); Associated with rhabdoid tumor predisposition syndrome 2.

What condition is associated with SMARCA4 p.Asp86= (c.258C>T)?

SMARCA4 p.Asp86= (c.258C>T) is associated with rhabdoid tumor predisposition syndrome 2, intellectual disability, autosomal dominant 16, hereditary neoplastic syndrome (ClinVar).

How common is SMARCA4 p.Asp86= (c.258C>T) in the general population?

SMARCA4 p.Asp86= (c.258C>T) is rare (popmax 0.487%, afr) (gnomAD).

How is Rhabdoid tumor predisposition syndrome inherited?

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

SMARCA4 p.Asp86=

c.258C>T · rs115992445 · VCV415145

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.487%, afr)

Conditions

rhabdoid tumor predisposition syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.3	GERP -4.4
Overall
CADD	0.576	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.487% African / African-American · 365/75,008 alleles

Filtering AF 0.445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.429%

Overall 0.0293% 473/1,614,012 alleles · rare exomes 254/1,461,796 · genomes 219/152,216 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.487%	206
Middle Eastern	0.066%	1,516
South Asian	0.0417%	2,397
Admixed American	0.03%	3,335
Remaining individualsnot grpmax-eligible	0.0256%	3,907
East Asian	0.0111%	8,971
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.0022%	45,384

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.Asp86=
Coding: c.258C>T
MANE Select: NM_003072
dbSNP: rs115992445
Type: single nucleotide variant
Location: chr19:10985308 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 86: 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

Also linked: intellectual disability, autosomal dominant 16 hereditary neoplastic syndrome

For Rhabdoid tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

SMARCA4 p.Asp86Gly Uncertain significance ★★ ⚠ same residue
SMARCA4 p.Asp86Asn 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

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-asp86 (accessed [today's date]).

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