CLCN6 p.Ala775=
c.2325C>T · rs762797912 · VCV1909516
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0067%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.70 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9.4 | GERP -3.1 |
| Overall | ||
| CADD | 8.193 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0067%
Admixed American · 4/59,738 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.00223%
36/1,612,514 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0067% | 14,934 |
| East Asian | 0.00447% | 22,374 |
| South Asian | 0.0033% | 30,259 |
| European (non-Finnish) | 0.00212% | 47,184 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,440 |
| Finnishnot grpmax-eligible | 0.00157% | 63,812 |
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.Ala775=
- Coding
- c.2325C>T
- MANE Select
- NM_001286
- dbSNP
- rs762797912
- Type
- single nucleotide variant
- Location
- chr1:11838364 (GRCh38)
- Gene constraint
- LOEUF 0.787 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.43 · 3 PDB
- Residue 775
- an α-helix
Similar variants
- 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
- CLCN6 p.Ala78Val 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-ala775 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown