SMARCB1 p.Arg261=
c.783C>A · rs748964274 · VCV1103902
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00934%, afr)
Conditions
1
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 -5.2 | GERP -3.5 |
| Overall | ||
| CADD | 1.307 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00934%
African / African-American · 7/74,924 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00309%
Overall
0.000434%
7/1,613,822 alleles · very rare
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
- SMARCB1
- Protein
- p.Arg261=
- Coding
- c.783C>A
- MANE Select
- NM_003073
- dbSNP
- rs748964274
- Type
- single nucleotide variant
- Location
- chr22:23816924 (GRCh38)
- Gene constraint
- LOEUF 0.221 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.77 · 17 PDB
- Residue 261
- a β-strand; the '2 x approximate tandem repeats' region
Similar variants
- SMARCB1 p.Arg261Cys Uncertain significance ★★ ⚠ same residue
- SMARCB1 p.Arg261His Uncertain significance ★★ ⚠ same residue
- SMARCB1 p.Arg261Ser Uncertain significance ★★ ⚠ same residue
- SMARCB1 c.795+1G>A Likely pathogenic ★★ same condition
- SMARCB1 c.93+1G>A Likely pathogenic ★★ same condition
- SMARCB1 c.986+1G>A Likely pathogenic ★★ same condition
- SMARCB1 c.*82C>T Pathogenic/Likely pathogenic ★★ same condition
- SMARCB1 p.Arg158Ter 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/smarcb1-p-arg261 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown