SMARCC2 p.Pro146=
c.438A>G · rs7136420 · VCV1275316
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 11.2%, afr) — too common for a highly-penetrant pathogenic allele
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 0.25 | GERP -1.6, phastCons 0.99 |
| Overall | ||
| CADD | 9.448 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.2%
African / African-American · 8,421/74,910 alleles
Filtering AF
11%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 11%
Overall
0.623%
10,052/1,613,582 alleles · common
exomes 5,049/1,461,402 · genomes 5,003/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 11.2% | 9 |
| Middle Eastern | 1.17% | 85 |
| Remaining individualsnot grpmax-eligible | 0.859% | 116 |
| Admixed American | 0.838% | 119 |
| Ashkenazi Jewishnot grpmax-eligible | 0.598% | 167 |
| South Asian | 0.0428% | 2,335 |
| European (non-Finnish) | 0.0255% | 3,919 |
| Finnishnot grpmax-eligible | 0.00468% | 21,347 |
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
- SMARCC2
- Protein
- p.Pro146=
- Coding
- c.438A>G
- MANE Select
- NM_001330288
- dbSNP
- rs7136420
- Type
- single nucleotide variant
- Location
- chr12:56184898 (GRCh38)
- Gene constraint
- LOEUF 0.167 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 64.89 · 9 PDB
- Residue 146
- the brct; n-terminus domain; the 'marr-like, brct and chromo domains module' region
Similar variants
- SMARCC2 c.1311-3C>G Pathogenic/Likely pathogenic ★★ same type
- SMARCC2 c.1926+1G>A Pathogenic/Likely pathogenic ★★ same type
- SMARCC2 c.1926+1G>T Pathogenic/Likely pathogenic ★★ same type
- SMARCC2 c.1926+2T>C Pathogenic/Likely pathogenic ★★ same type
- SMARCC2 p.Arg116His Likely pathogenic ★★ same type
- SMARCC2 p.Arg192Ter Pathogenic/Likely pathogenic ★★ same type
- SMARCC2 p.Arg269Ter Pathogenic/Likely pathogenic ★★ same type
- SMARCC2 p.Arg474Ter Pathogenic/Likely pathogenic ★★ same type
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/smarcc2-p-pro146 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown