CLCN7 p.Pro304=
c.912C>T · rs41286693 · VCV1142546
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00967%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.2 | GERP -3.9 |
| Overall | ||
| CADD | 8.144 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00967%
East Asian · 4/41,360 alleles
Filtering AF
0.00325%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00192%
Overall
0.00167%
26/1,554,648 alleles · very rare
exomes 23/1,402,296 · genomes 3/152,352 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00967% | 10,340 |
| European (non-Finnish) | 0.00183% | 54,719 |
| African / African-American | 0.00136% | 73,460 |
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.Pro304=
- Coding
- c.912C>T
- MANE Select
- NM_001287
- dbSNP
- rs41286693
- Type
- single nucleotide variant
- Location
- chr16:1456117 (GRCh38)
- Gene constraint
- LOEUF 0.821 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.94 · 9 PDB
- Residue 304
- an α-helix
Similar variants
- 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
- CLCN7 p.Arg55Ter 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-pro304 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown