CLCN7 p.Pro481=
c.1443G>A · rs372732179 · VCV1546439
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0176%, 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 -6.4 | GERP -3 |
| Overall | ||
| CADD | 0.353 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0176%
South Asian · 16/91,044 alleles
Filtering AF
0.0141%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0134%
Overall
0.0137%
220/1,611,016 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0176% | 5,690 |
| European (non-Finnish) | 0.016% | 6,241 |
| African / African-American | 0.0107% | 9,361 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,492 |
| East Asian | 0.00223% | 44,858 |
| Finnishnot grpmax-eligible | 0.00162% | 61,588 |
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
- CLCN7
- Protein
- p.Pro481=
- Coding
- c.1443G>A
- MANE Select
- NM_001287
- dbSNP
- rs372732179
- Type
- single nucleotide variant
- Location
- chr16:1451627 (GRCh38)
- Gene constraint
- LOEUF 0.821 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.94 · 9 PDB
Similar variants
- CLCN7 p.Pro481Leu Uncertain significance ★ ⚠ same residue
- CLCN7 c.1448-2A>G Likely pathogenic ★★ same type
- CLCN7 c.1617+119G>A Pathogenic ★★ same type
- CLCN7 c.739-18G>A Pathogenic/Likely pathogenic ★★ same type
- CLCN7 p.Arg286Gln Pathogenic/Likely pathogenic ★★ same type
- CLCN7 p.Arg286Trp Pathogenic/Likely pathogenic ★★ same type
- CLCN7 p.Arg526Gln Likely pathogenic ★★ same type
- CLCN7 p.Arg526Trp Pathogenic/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/clcn7-p-pro481 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown