SCNN1B p.Pro18=
c.54C>T · rs144142075 · VCV2716725
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0308%, sas)
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 -20 | GERP -3.6 |
| Overall | ||
| CADD | 3.247 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0308%
South Asian · 28/91,046 alleles
Filtering AF
0.0218%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0188%
Overall
0.00353%
57/1,613,518 alleles · ultra-rare
exomes 48/1,461,354 · genomes 9/152,164 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0308% | 3,252 |
| Admixed American | 0.0167% | 5,999 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,486 |
| East Asian | 0.00446% | 22,439 |
| African / African-American | 0.00133% | 74,920 |
| European (non-Finnish) | 0.000932% | 107,272 |
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
- SCNN1B
- Protein
- p.Pro18=
- Coding
- c.54C>T
- MANE Select
- NM_000336
- dbSNP
- rs144142075
- Type
- single nucleotide variant
- Location
- chr16:23348653 (GRCh38)
- Gene constraint
- LOEUF 0.81 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.96 · 5 PDB
Similar variants
- SCNN1B c.1542+1G>A Pathogenic/Likely pathogenic ★★ same type
- SCNN1B p.Arg566Ter Pathogenic ★★ same type
- SCNN1B p.Pro616Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
- SCNN1B p.Pro617Ser Pathogenic/Likely pathogenic ★★ same type
- SCNN1B p.Pro618Ser Pathogenic/Likely pathogenic ★★ same type
- SCNN1B c.1270+6C>T Uncertain significance ★★ same type
- SCNN1B c.585+3A>C Uncertain significance ★★ same type
- SCNN1B c.776+3G>A 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/scnn1b-p-pro18 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown