CLCN2 p.Ile211=
c.633C>T · VCV3631951
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
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 -5.4 | GERP -2.8 |
| Overall | ||
| CADD | 0.468 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,886 alleles
Filtering AF
0.00689%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00633%
Overall
0.00682%
110/1,613,856 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,977 |
| European (non-Finnish) | 0.00822% | 12,165 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| Finnishnot grpmax-eligible | 0.0047% | 21,267 |
| African / African-American | 0.00267% | 37,465 |
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.Ile211=
- Coding
- c.633C>T
- MANE Select
- NM_004366
- Type
- single nucleotide variant
- Location
- chr3:184357839 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 8 PDB
- Residue 211
- an α-helix
Similar variants
- CLCN2 p.Ile211Met Uncertain significance ★★ ⚠ same residue
- CLCN2 p.Ile211Val 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-ile211 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown