CLCN4 p.Leu693=
c.2077C>T · rs771277540 · VCV1552756
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00437%, amr)
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 2.7 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 7.494 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00437%
Admixed American · 2/45,793 alleles
Filtering AF
0.000724%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000271%
Overall
0.000248%
3/1,209,810 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00437% | 22,896 |
| European (non-Finnish) | 0.000112% | 894,895 |
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.Leu693=
- Coding
- c.2077C>T
- MANE Select
- NM_001830
- dbSNP
- rs771277540
- Type
- single nucleotide variant
- Location
- chrX:10220762 (GRCh38)
- Structure
- AlphaFold pLDDT 84.66
- Residue 693
- the 'required for localization in the endoplasmic reticulum' region
Similar variants
- CLCN4 p.Leu693Met 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-leu693 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown