CLCN2 p.Cys69=
c.207C>T · VCV3652678
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0106%, 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 -3.5 | GERP -2.6 |
| Overall | ||
| CADD | 0.754 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0106%
European (non-Finnish) · 125/1,180,036 alleles
Filtering AF
0.00906%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00844%
Overall
0.00855%
138/1,613,448 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0106% | 9,440 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,495 |
| Finnishnot grpmax-eligible | 0.00789% | 12,681 |
| African / African-American | 0.00267% | 37,467 |
| South Asian | 0.0011% | 91,090 |
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
- CLCN2
- Protein
- p.Cys69=
- Coding
- c.207C>T
- MANE Select
- NM_004366
- Type
- single nucleotide variant
- Location
- chr3:184358988 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 8 PDB
Similar variants
- CLCN2 p.Cys69Ter Likely pathogenic ★ same residue
- CLCN2 p.Cys69Phe Uncertain significance ★ same residue
- CLCN2 c.898+1G>A Likely pathogenic ★★ same type
- CLCN2 p.Arg172Gln Pathogenic ★★ same type
- CLCN2 p.Arg610Ter Pathogenic/Likely pathogenic ★★ same type
- CLCN2 p.Glu619Ter Pathogenic/Likely pathogenic ★★ same type
- CLCN2 p.Gly24Asp Pathogenic/Likely pathogenic ★★ ⚠ same type
- CLCN2 p.Trp570Ter Pathogenic/Likely pathogenic ★★ 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/clcn2-p-cys69 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown