CLCN2 p.Arg800=
c.2400G>T · rs145544948 · VCV2037980
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0854%, afr)
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 -0.66 | GERP -0.67, phastCons 0.009 |
| Overall | ||
| CADD | 6.381 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0854%
African / African-American · 64/74,982 alleles
Filtering AF
0.0686%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0625%
Overall
0.0049%
79/1,613,650 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0854% | 1,172 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,813 |
| Admixed American | 0.01% | 10,000 |
| European (non-Finnish) | 8.48e-05% | 1,179,883 |
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.Arg800=
- Coding
- c.2400G>T
- MANE Select
- NM_004366
- dbSNP
- rs145544948
- Type
- single nucleotide variant
- Location
- chr3:184352028 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 8 PDB
- Residue 800
- the cbs 2 domain; a UniProt-annotated variant site (in lkpat; decreased voltage-gated chloride channel activity; does not affect protein expression; does not affect localization at the cell membrane)
Similar variants
- CLCN2 p.Arg800Trp Uncertain significance ★★ ⚠ same residue
- CLCN2 p.Arg800Gln 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-arg800 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown