CLCN5 p.Pro638=
c.1914C>T · rs34173954 · VCV368486
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 21.4%, afr) — too common for a highly-penetrant pathogenic allele
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 0.086 | GERP -0.023, phastCons 0.9 |
| Overall | ||
| CADD | 12.91 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
21.4%
African / African-American · 12,198/56,924 alleles
Filtering AF
21.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 21%
Overall
1.13%
13,620/1,209,504 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 21.4% | 5 |
| Remaining individualsnot grpmax-eligible | 1.36% | 74 |
| Admixed American | 1.2% | 84 |
| Middle Eastern | 0.759% | 132 |
| South Asian | 0.0423% | 2,366 |
| European (non-Finnish) | 0.019% | 5,264 |
| Finnishnot grpmax-eligible | 0.00214% | 46,669 |
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.Pro638=
- Coding
- c.1914C>T
- MANE Select
- NM_001127898
- dbSNP
- rs34173954
- Type
- single nucleotide variant
- Location
- chrX:50090285 (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-pro638 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown