CLCN2 p.Ser716=
c.2148C>T · rs143478108 · VCV1660471
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.25 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.47 | GERP -3.4 |
| Overall | ||
| CADD | 1.015 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
African / African-American · 15/75,062 alleles
Filtering AF
0.0149%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0142%
Overall
0.0138%
222/1,613,196 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.02% | 5,004 |
| European (non-Finnish) | 0.0169% | 5,929 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,500 |
| Admixed American | 0.00167% | 60,010 |
| Finnishnot grpmax-eligible | 0.00158% | 63,142 |
| South Asian | 0.0011% | 91,084 |
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.Ser716=
- Coding
- c.2148C>T
- MANE Select
- NM_004366
- dbSNP
- rs143478108
- Type
- single nucleotide variant
- Location
- chr3:184352806 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 8 PDB
- Residue 716
- the 'disordered' region
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-ser716 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown