SMARCC2 p.Arg474Ter
c.1420C>T · VCV3342316
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Coffin-Siris syndrome 8
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 16 of 29 |
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.43 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 8.6 | GERP 0.78, phastCons 1 |
| Overall | ||
| CADD | 38.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- SMARCC2
- Protein
- p.Arg474Ter
- Coding
- c.1420C>T
- MANE Select
- NM_001330288
- Type
- single nucleotide variant
- Location
- chr12:56174727 (GRCh38)
- Gene constraint
- LOEUF 0.167 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 64.89 · 9 PDB
- Residue 474
- a UniProt-annotated variant site (in css8); the swirm domain; an α-helix
Similar variants
- SMARCC2 c.1311-3C>G Pathogenic/Likely pathogenic ★★ same condition
- SMARCC2 c.1926+1G>A Pathogenic/Likely pathogenic ★★ same condition
- SMARCC2 c.1926+1G>T Pathogenic/Likely pathogenic ★★ same condition
- SMARCC2 c.1926+2T>C Pathogenic/Likely pathogenic ★★ same condition
- SMARCC2 p.Arg192Ter Pathogenic/Likely pathogenic ★★ same condition
- SMARCC2 p.Arg269Ter Pathogenic/Likely pathogenic ★★ same condition
- SMARCC2 p.Glu924Gly Likely pathogenic ★★ same condition
- SMARCC2 p.Ala1033Asp Uncertain significance ★★ ⚠ 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/smarcc2-p-arg474ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown