CLCN6 p.Pro257=
c.771A>G · rs529897896 · VCV1930646
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.182%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.062 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.1 | GERP -3.4 |
| Overall | ||
| CADD | 0.907 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.182%
South Asian · 166/91,060 alleles
Filtering AF
0.16%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.151%
Overall
0.0107%
172/1,613,928 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.182% | 549 |
| Middle Eastern | 0.033% | 3,029 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,623 |
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
- CLCN6
- Protein
- p.Pro257=
- Coding
- c.771A>G
- MANE Select
- NM_001286
- dbSNP
- rs529897896
- Type
- single nucleotide variant
- Location
- chr1:11827152 (GRCh38)
- Gene constraint
- LOEUF 0.787 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.43 · 3 PDB
- Residue 257
- an α-helix
Similar variants
- CLCN6 p.Pro257Thr Uncertain significance ★ ⚠ same residue
- CLCN6 p.Tyr553Cys Pathogenic ★★ same type
- CLCN6 p.Ala127Thr Uncertain significance ★★ ⚠ same type
- CLCN6 p.Ala144Glu Uncertain significance ★★ ⚠ same type
- CLCN6 p.Ala256Val Uncertain significance ★★ ⚠ same type
- CLCN6 p.Ala392Val Uncertain significance ★★ ⚠ same type
- CLCN6 p.Ala522Thr Uncertain significance ★★ ⚠ same type
- CLCN6 p.Ala527Val Uncertain significance ★★ ⚠ 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/clcn6-p-pro257 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown