CLCN5 p.Glu645Ter
c.1933G>T · rs2519445104 · VCV2635308
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
CLCN5-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 13 of 15 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.8, phastCons 1 |
| Overall | ||
| CADD | 39.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CLCN5
- Protein
- p.Glu645Ter
- Coding
- c.1933G>T
- MANE Select
- NM_001127898
- dbSNP
- rs2519445104
- Type
- single nucleotide variant
- Location
- chrX:50090304 (GRCh38)
- Structure
- AlphaFold pLDDT 80.48 · 2 PDB
Disease context
CLCN5-related disorder
Similar variants
- CLCN5 p.Arg537Ter Pathogenic ★★ same condition
- CLCN5 p.Arg707Ter Pathogenic ★★ same condition
- CLCN5 p.Arg718Ter Pathogenic ★★ same condition
- CLCN5 p.Arg98Ter Pathogenic/Likely pathogenic ★★ same condition
- CLCN5 p.Gln421Ter Likely pathogenic ★★ same condition
- CLCN5 p.Ser314Leu Pathogenic ★★ same condition
- CLCN5 p.Ser615Asn Likely pathogenic ★★ same condition
- CLCN5 p.Tyr342Cys Pathogenic/Likely pathogenic ★★ same condition
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/clcn5-p-glu645ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown