CLCN4 p.Pro635=
c.1905C>T · rs749273690 · VCV1170927
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0415%, eas)
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 -4.3 |
| Overall | ||
| CADD | 0.015 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0415%
East Asian · 14/33,742 alleles
Filtering AF
0.0251%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0201%
Overall
0.00306%
37/1,207,337 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0415% | 2,410 |
| African / African-American | 0.00522% | 19,160 |
| European (non-Finnish) | 0.00213% | 47,034 |
| Remaining individualsnot grpmax-eligible | 0.00211% | 47,427 |
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
- CLCN4
- Protein
- p.Pro635=
- Coding
- c.1905C>T
- MANE Select
- NM_001830
- dbSNP
- rs749273690
- Type
- single nucleotide variant
- Location
- chrX:10214009 (GRCh38)
- Structure
- AlphaFold pLDDT 84.66
- Residue 635
- the cbs 1 domain
Similar variants
- CLCN4 p.Pro635Arg Uncertain significance ★ ⚠ same residue
- CLCN4 c.844-1G>A Pathogenic/Likely pathogenic ★★ same type
- CLCN4 p.Ala555Val Pathogenic ★★ ⚠ same type
- CLCN4 p.Arg718Trp Pathogenic ★★ same type
- CLCN4 p.Asp89Asn Pathogenic/Likely pathogenic ★★ ⚠ same type
- CLCN4 p.Gly467Ser Likely pathogenic ★★ same type
- CLCN4 p.Gly544Arg Pathogenic ★★ same type
- CLCN4 p.Gly731Arg 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/clcn4-p-pro635 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown