CLCN5 p.Ser140=
c.420G>A · rs376292808 · VCV1664148
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0105%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.83 | GERP -5.2 |
| Overall | ||
| CADD | 3.516 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0105%
African / African-American · 6/57,143 alleles
Filtering AF
0.00456%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00307%
Overall
0.00157%
19/1,208,660 alleles · ultra-rare
exomes 15/1,096,794 · genomes 4/111,866 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0105% | 9,524 |
| Remaining individualsnot grpmax-eligible | 0.0042% | 23,782 |
| Finnishnot grpmax-eligible | 0.00215% | 46,604 |
| European (non-Finnish) | 0.00112% | 89,404 |
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
- CLCN5
- Protein
- p.Ser140=
- Coding
- c.420G>A
- MANE Select
- NM_001127898
- dbSNP
- rs376292808
- Type
- single nucleotide variant
- Location
- chrX:50075799 (GRCh38)
- Structure
- AlphaFold pLDDT 80.48 · 2 PDB
Similar variants
- CLCN5 c.1014+1G>A Pathogenic/Likely pathogenic ★★ same type
- CLCN5 c.604-1G>C Likely pathogenic ★★ same type
- CLCN5 c.933+1G>A Pathogenic/Likely pathogenic ★★ same type
- CLCN5 p.Arg104Ter Pathogenic/Likely pathogenic ★★ same type
- CLCN5 p.Arg417Ter Pathogenic ★★ same type
- CLCN5 p.Arg537Ter Pathogenic ★★ same type
- CLCN5 p.Arg586Trp Pathogenic/Likely pathogenic ★★ same type
- CLCN5 p.Arg707Ter 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/clcn5-p-ser140 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown