CLCNKB p.Pro517=
c.1551C>G · rs750352082 · VCV1557791
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00768%, sas)
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 -1.4 | GERP -0.19 |
| Overall | ||
| CADD | 5.505 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00768%
South Asian · 7/91,090 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00255%
Overall
0.00298%
48/1,613,104 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00768% | 13,013 |
| European (non-Finnish) | 0.0033% | 30,258 |
| African / African-American | 0.00267% | 37,465 |
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
- CLCNKB
- Protein
- p.Pro517=
- Coding
- c.1551C>G
- MANE Select
- NM_000085
- dbSNP
- rs750352082
- Type
- single nucleotide variant
- Location
- chr1:16052340 (GRCh38)
- Gene constraint
- LOEUF 1.072 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.16
Similar variants
- CLCNKB c.968+1G>A Pathogenic/Likely pathogenic ★★ same type
- CLCNKB p.Ala204Thr Pathogenic/Likely pathogenic ★★ same type
- CLCNKB p.Ala77Pro Pathogenic/Likely pathogenic ★★ same type
- CLCNKB p.Arg304Ter Pathogenic/Likely pathogenic ★★ same type
- CLCNKB p.Arg438His Pathogenic ★★ same type
- CLCNKB p.Arg595Ter Pathogenic ★★ same type
- CLCNKB p.Arg76Ter Pathogenic ★★ same type
- CLCNKB p.Glu225Ter 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/clcnkb-p-pro517 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown