CLCN7 p.Pro80=
c.240C>T · rs937528179 · VCV1620883
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
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 2.9 | GERP -2.4, phastCons 1 |
| Overall | ||
| CADD | 11.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,894 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.00062%
10/1,614,014 alleles · very rare
exomes 8/1,461,838 · genomes 2/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,965 |
| European (non-Finnish) | 0.000593% | 168,576 |
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.Pro80=
- Coding
- c.240C>T
- MANE Select
- NM_001287
- dbSNP
- rs937528179
- Type
- single nucleotide variant
- Location
- chr16:1461648 (GRCh38)
- Gene constraint
- LOEUF 0.821 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.94 · 9 PDB
Similar variants
- CLCN7 p.Pro80Leu Uncertain significance ★★ ⚠ same residue
- CLCN7 p.Pro80Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
- CLCN7 p.Pro80Thr 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
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-pro80 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown