CLCN6 p.Asp40=
c.120T>C · rs377627467 · VCV2196413
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0112%, nfe)
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 0.67 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 11.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0112%
European (non-Finnish) · 132/1,177,376 alleles
Filtering AF
0.00963%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00906%
Overall
0.00838%
135/1,611,000 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0112% | 8,919 |
| Admixed American | 0.00167% | 59,976 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,370 |
| African / African-American | 0.00134% | 74,846 |
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.Asp40=
- Coding
- c.120T>C
- MANE Select
- NM_001286
- dbSNP
- rs377627467
- Type
- single nucleotide variant
- Location
- chr1:11807163 (GRCh38)
- Gene constraint
- LOEUF 0.787 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.43 · 3 PDB
Similar variants
- CLCN6 p.Asp40Glu Uncertain significance ★ ⚠ same residue
- CLCN6 p.Asp40Ala 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
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-asp40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown