SMARCA5 p.Phe391=
c.1173C>T · VCV3905421
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0755%, amr)
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 0.13 | GERP 0.21, phastCons 0.94 |
| Overall | ||
| CADD | 8.461 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0755%
Admixed American · 45/59,638 alleles
Filtering AF
0.0579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0518%
Overall
0.00323%
52/1,611,786 alleles · ultra-rare
exomes 34/1,459,614 · genomes 18/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0755% | 1,325 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,382 |
| South Asian | 0.0011% | 90,620 |
| European (non-Finnish) | 0.000424% | 235,807 |
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
- SMARCA5
- Protein
- p.Phe391=
- Coding
- c.1173C>T
- MANE Select
- NM_003601
- Type
- single nucleotide variant
- Location
- chr4:143534869 (GRCh38)
- Gene constraint
- LOEUF 0.222 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 75.41 · 15 PDB
- Residue 391
- an α-helix
Similar variants
- SMARCA5 p.Glu893Lys Pathogenic ★★ same type
- SMARCA5 p.Pro339Ser Likely pathogenic ★★ same type
- SMARCA5 p.Lys694Glu Uncertain significance ★★ ⚠ same type
- SMARCA5 p.Met386Thr Uncertain significance ★★ ⚠ same type
- SMARCA5 p.Ala51= Likely benign ★★ same type
- SMARCA5 p.Phe92= Benign ★★ same type
- SMARCA5 p.Ser26= Benign/Likely benign ★★ same type
- SMARCA5 c.2283+1G>A 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/smarca5-p-phe391 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown