CLCN7 p.Pro249=
c.747G>A · rs199790407 · VCV747843
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.178%, 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 -9.3 | GERP -3 |
| Overall | ||
| CADD | 4.107 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.178%
South Asian · 162/91,052 alleles
Filtering AF
0.156%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.147%
Overall
0.0336%
542/1,613,530 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.178% | 562 |
| Admixed American | 0.137% | 732 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| Middle Eastern | 0.033% | 3,026 |
| European (non-Finnish) | 0.0225% | 4,452 |
| East Asian | 0.00891% | 11,220 |
| African / African-American | 0.004% | 25,021 |
| Finnishnot grpmax-eligible | 0.00314% | 31,850 |
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.Pro249=
- Coding
- c.747G>A
- MANE Select
- NM_001287
- dbSNP
- rs199790407
- Type
- single nucleotide variant
- Location
- chr16:1457329 (GRCh38)
- Gene constraint
- LOEUF 0.821 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.94 · 9 PDB
- Residue 249
- a UniProt-annotated variant site (in optb4); an α-helix
Similar variants
- CLCN7 p.Pro249Arg Pathogenic/Likely pathogenic ★★ same residue
- CLCN7 p.Pro249Leu Pathogenic ★★ same residue
- CLCN7 p.Pro249Gln 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
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-pro249 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown