CLCN2 p.Pro367=
c.1101G>A · rs3749221 · VCV1224803
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 6.32%, eas) — too common for a highly-penetrant pathogenic allele
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 -10 | GERP -3.7 |
| Overall | ||
| CADD | 8.401 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.32%
East Asian · 2,837/44,864 alleles
Filtering AF
6.13%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.05%
Overall
2.37%
38,313/1,614,002 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 6.32% | 16 |
| Ashkenazi Jewishnot grpmax-eligible | 4.86% | 21 |
| Amishnot grpmax-eligible | 4.28% | 23 |
| Middle Eastern | 3.94% | 25 |
| European (non-Finnish) | 2.49% | 40 |
| Remaining individualsnot grpmax-eligible | 2.45% | 41 |
| South Asian | 1.26% | 79 |
| Admixed American | 1.19% | 84 |
| Finnishnot grpmax-eligible | 1.06% | 94 |
| African / African-American | 0.425% | 235 |
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.Pro367=
- Coding
- c.1101G>A
- MANE Select
- NM_004366
- dbSNP
- rs3749221
- Type
- single nucleotide variant
- Location
- chr3:184355763 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 8 PDB
- Residue 367
- an α-helix
Similar variants
- CLCN2 p.Pro367Leu 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
- CLCN2 c.1171-3T>C 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/clcn2-p-pro367 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown