CLCNKB p.Pro500=
c.1500C>T · rs779635426 · VCV2974441
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0374%, afr)
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 -20 | GERP -4.4 |
| Overall | ||
| CADD | 0.122 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0374%
African / African-American · 28/74,932 alleles
Filtering AF
0.0265%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0229%
Overall
0.00304%
49/1,613,222 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0374% | 2,676 |
| Admixed American | 0.005% | 20,004 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| South Asian | 0.00329% | 30,360 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,240 |
| European (non-Finnish) | 0.00102% | 98,337 |
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.Pro500=
- Coding
- c.1500C>T
- MANE Select
- NM_000085
- dbSNP
- rs779635426
- Type
- single nucleotide variant
- Location
- chr1:16052289 (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 p.Pro500Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro500 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown