CLCN7 p.Ala511=
c.1533C>T · rs374608288 · VCV1601832
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0264%, 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 -7.6 | GERP -3.6 |
| Overall | ||
| CADD | 3.576 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0264%
South Asian · 24/90,934 alleles
Filtering AF
0.0181%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0154%
Overall
0.015%
242/1,612,204 alleles · ultra-rare
exomes 228/1,459,990 · genomes 14/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0264% | 3,789 |
| European (non-Finnish) | 0.017% | 5,899 |
| Admixed American | 0.015% | 6,658 |
| African / African-American | 0.00934% | 10,703 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,211 |
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.Ala511=
- Coding
- c.1533C>T
- MANE Select
- NM_001287
- dbSNP
- rs374608288
- Type
- single nucleotide variant
- Location
- chr16:1450581 (GRCh38)
- Gene constraint
- LOEUF 0.821 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.94 · 9 PDB
Similar variants
- CLCN7 p.Ala511Pro 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-ala511 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown