CLCN7 p.Ser753=
c.2259G>A · rs146048095 · VCV1095000
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0331%, mid)
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 -4 | GERP -3 |
| Overall | ||
| CADD | 0.311 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0331%
Middle Eastern · 2/6,038 alleles
Filtering AF
0.00759%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00708%
Overall
0.00763%
122/1,598,334 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0331% | 3,019 |
| Admixed American | 0.0101% | 9,895 |
| Remaining individualsnot grpmax-eligible | 0.00967% | 10,344 |
| European (non-Finnish) | 0.00901% | 11,103 |
| East Asian | 0.00225% | 44,442 |
| South Asian | 0.00111% | 89,820 |
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
- CLCN7
- Protein
- p.Ser753=
- Coding
- c.2259G>A
- MANE Select
- NM_001287
- dbSNP
- rs146048095
- Type
- single nucleotide variant
- Location
- chr16:1447078 (GRCh38)
- Gene constraint
- LOEUF 0.821 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.94 · 9 PDB
- Residue 753
- the cbs 2 domain
Similar variants
- CLCN7 p.Ser753Leu Uncertain significance ★ ⚠ same residue
- CLCN7 c.1448-2A>G Likely pathogenic ★★ same type
- CLCN7 c.1617+119G>A Pathogenic ★★ same type
- CLCN7 c.739-18G>A Pathogenic/Likely pathogenic ★★ same type
- CLCN7 p.Arg286Gln Pathogenic/Likely pathogenic ★★ same type
- CLCN7 p.Arg286Trp Pathogenic/Likely pathogenic ★★ same type
- CLCN7 p.Arg526Gln Likely pathogenic ★★ same type
- CLCN7 p.Arg526Trp 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/clcn7-p-ser753 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown