SLC12A3 p.Pro331fs
c.990_1005del · VCV4818217
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
Gitelman syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 8 of 26 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2.6, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- SLC12A3
- Protein
- p.Pro331fs
- Coding
- c.990_1005del
- MANE Select
- NM_001126108
- Type
- Deletion
- Location
- chr16:56872678 (GRCh38)
- Gene constraint
- LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.94 · 12 PDB
Disease context
Gitelman syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Gitelman syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- SLC12A3 c.1335+1_1335+6del Likely pathogenic ★★ same condition
- SLC12A3 c.2039delG Pathogenic ★★ same condition
- SLC12A3 c.2368+2del Pathogenic/Likely pathogenic ★★ same condition
- SLC12A3 c.429+1_429+28del Pathogenic/Likely pathogenic ★★ same condition
- SLC12A3 p.Ala224fs Pathogenic/Likely pathogenic ★★ same condition
- SLC12A3 p.Ala251fs Pathogenic/Likely pathogenic ★★ same condition
- SLC12A3 p.Ala420fs Pathogenic/Likely pathogenic ★★ same condition
- SLC12A3 p.Arg19fs 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/slc12a3-p-pro331fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown