CLCN6 p.Ala78=
c.234G>A · rs57044879 · VCV1647653
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 10.7%, afr) — too common for a highly-penetrant pathogenic allele
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 -3.1 | GERP -3.3 |
| Overall | ||
| CADD | 7.461 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
10.7%
African / African-American · 8,054/74,976 alleles
Filtering AF
10.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.5%
Overall
0.61%
9,833/1,613,024 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 10.7% | 9 |
| Remaining individualsnot grpmax-eligible | 0.941% | 106 |
| Ashkenazi Jewishnot grpmax-eligible | 0.771% | 130 |
| Admixed American | 0.701% | 143 |
| Middle Eastern | 0.561% | 178 |
| South Asian | 0.0705% | 1,419 |
| East Asian | 0.0468% | 2,136 |
| European (non-Finnish) | 0.0359% | 2,788 |
| Finnishnot grpmax-eligible | 0.00156% | 63,944 |
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.Ala78=
- Coding
- c.234G>A
- MANE Select
- NM_001286
- dbSNP
- rs57044879
- Type
- single nucleotide variant
- Location
- chr1:11816635 (GRCh38)
- Gene constraint
- LOEUF 0.787 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.43 · 3 PDB
- Residue 78
- an α-helix
Similar variants
- CLCN6 p.Ala78Val 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-ala78 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown