CLCN6 p.Ala504=
c.1512C>G · rs1644912786 · VCV1652618
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00533%, afr)
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 3.2 | GERP 0.56, phastCons 1 |
| Overall | ||
| CADD | 11.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00533%
African / African-American · 4/74,996 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00031%
5/1,613,940 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00533% | 18,749 |
| European (non-Finnish) | 8.47e-05% | 1,179,980 |
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.Ala504=
- Coding
- c.1512C>G
- MANE Select
- NM_001286
- dbSNP
- rs1644912786
- Type
- single nucleotide variant
- Location
- chr1:11834016 (GRCh38)
- Gene constraint
- LOEUF 0.787 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.43 · 3 PDB
- Residue 504
- an α-helix
Similar variants
- CLCN6 p.Ala504Ser 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-ala504 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown