SCNN1A p.Ser261=
c.783G>A · rs72645110 · VCV737132
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.33 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP -4.6 |
| Overall | ||
| CADD | 4.594 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/60,014 alleles
Filtering AF
0.009%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00681%
Overall
0.0018%
29/1,614,082 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 6,001 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,497 |
| East Asian | 0.00445% | 22,448 |
| African / African-American | 0.004% | 24,975 |
| European (non-Finnish) | 0.000763% | 131,114 |
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
- SCNN1A
- Protein
- p.Ser261=
- Coding
- c.783G>A
- MANE Select
- NM_001038
- dbSNP
- rs72645110
- Type
- single nucleotide variant
- Location
- chr12:6362143 (GRCh38)
- Gene constraint
- LOEUF 1.105 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.66 · 3 PDB
- Residue 261
- a disulfide bond
Similar variants
- SCNN1A c.1360+2T>G Pathogenic ★★ same type
- SCNN1A c.1439+1G>A Pathogenic/Likely pathogenic ★★ same type
- SCNN1A c.685-1G>A Likely pathogenic ★★ same type
- SCNN1A c.875+1G>A Pathogenic/Likely pathogenic ★★ same type
- SCNN1A p.Arg492Ter Pathogenic ★★ same type
- SCNN1A p.Arg508Ter Pathogenic/Likely pathogenic ★★ same type
- SCNN1A p.Arg56Ter Pathogenic ★★ same type
- SCNN1A c.-23C>G 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/scnn1a-p-ser261 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown