CLCN7 p.Pro716=
c.2148G>A · rs149081153 · VCV712845
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.46%, afr)
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 -9.1 | GERP -3 |
| Overall | ||
| CADD | 0.404 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.46%
African / African-American · 1,069/73,290 alleles
Filtering AF
1.39%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.36%
Overall
0.0789%
1,226/1,553,484 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.46% | 69 |
| Remaining individualsnot grpmax-eligible | 0.108% | 926 |
| Admixed American | 0.0834% | 1,199 |
| Middle Eastern | 0.05% | 1,999 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00698% | 14,334 |
| South Asian | 0.00593% | 16,862 |
| European (non-Finnish) | 0.00331% | 30,230 |
| East Asian | 0.00243% | 41,092 |
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.Pro716=
- Coding
- c.2148G>A
- MANE Select
- NM_001287
- dbSNP
- rs149081153
- Type
- single nucleotide variant
- Location
- chr16:1447494 (GRCh38)
- Gene constraint
- LOEUF 0.821 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.94 · 9 PDB
Similar variants
- CLCN7 p.Pro716_Arg717insTer Likely pathogenic ★★ 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-pro716 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown