CLCN2 p.Val502=
c.1506C>G · rs762339307 · VCV2153759
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00666%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.367 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.52 | donor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -3.4 |
| Overall | ||
| CADD | 8.527 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00666%
Admixed American · 4/60,024 alleles
Filtering AF
0.00225%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.000548%
8/1,460,044 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00666% | 15,006 |
| South Asian | 0.0011% | 91,064 |
| European (non-Finnish) | 0.000254% | 393,066 |
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.Val502=
- Coding
- c.1506C>G
- MANE Select
- NM_004366
- dbSNP
- rs762339307
- Type
- single nucleotide variant
- Location
- chr3:184354549 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 8 PDB
- Residue 502
- an α-helix
Similar variants
- 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
- CLCN2 c.1721+4C>T 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-val502 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown