SMARCA1 p.Arg253=
c.759A>G · VCV3899527
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000224%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.60 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.46 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.89 | GERP -3.3, phastCons 1 |
| Overall | ||
| CADD | 19.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000224%
European (non-Finnish) · 2/891,230 alleles
Filtering AF
3.7e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.4e-05%
Overall
0.000166%
2/1,204,598 alleles · very rare
exomes 1/1,092,231 · genomes 1/112,367 · joint denominator
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
- SMARCA1
- Protein
- p.Arg253=
- Coding
- c.759A>G
- MANE Select
- NM_001282874
- Type
- single nucleotide variant
- Location
- chrX:129511855 (GRCh38)
- Structure
- AlphaFold pLDDT 75.48
- Residue 253
- the helicase atp-binding domain
Similar variants
- SMARCA1 p.Arg253Ter Likely pathogenic ★ same residue
- SMARCA1 p.Ala39Thr Uncertain significance ★★ ⚠ same type
- SMARCA1 p.Ala48Glu Uncertain significance ★★ ⚠ same type
- SMARCA1 p.Ala6Pro Uncertain significance ★★ ⚠ same type
- SMARCA1 p.Arg751Gln Uncertain significance ★★ ⚠ same type
- SMARCA1 p.Asp721Asn Uncertain significance ★★ same type
- SMARCA1 p.Gly30Arg Uncertain significance ★★ ⚠ same type
- SMARCA1 p.Lys680Glu Uncertain significance ★★ 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/smarca1-p-arg253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown