CLCN2 p.Arg73=
c.219C>T · rs749161399 · VCV1415545
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
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 3.9 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 12.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,080 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.00105%
17/1,613,246 alleles · very rare
exomes 15/1,461,148 · genomes 2/152,098 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,360 |
| African / African-American | 0.00267% | 37,448 |
| East Asian | 0.00223% | 44,890 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,470 |
| European (non-Finnish) | 0.000847% | 117,996 |
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.Arg73=
- Coding
- c.219C>T
- MANE Select
- NM_004366
- dbSNP
- rs749161399
- Type
- single nucleotide variant
- Location
- chr3:184358976 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 8 PDB
Similar variants
- CLCN2 p.Arg73Cys Uncertain significance ★ ⚠ same residue
- CLCN2 p.Arg73His Conflicting classifications of pathogenicity ★ ⚠ 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-arg73 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown