CLCN6 p.Phe97=
c.291T>C · rs776926711 · VCV1603539
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.14%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.24 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP -3.2 |
| Overall | ||
| CADD | 1.893 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.14%
Admixed American · 84/60,006 alleles
Filtering AF
0.116%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.107%
Overall
0.00539%
87/1,614,084 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.14% | 714 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,245 |
| European (non-Finnish) | 8.47e-05% | 1,180,025 |
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.Phe97=
- Coding
- c.291T>C
- MANE Select
- NM_001286
- dbSNP
- rs776926711
- Type
- single nucleotide variant
- Location
- chr1:11819499 (GRCh38)
- Gene constraint
- LOEUF 0.787 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.43 · 3 PDB
- Residue 97
- an α-helix
Similar variants
- CLCN6 p.Phe97Ser 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-phe97 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown