SLC12A2 p.Phe372=
c.1116C>T · VCV4709493
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0668%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5 | GERP -5.9 |
| Overall | ||
| CADD | 7.834 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0668%
East Asian · 30/44,882 alleles
Filtering AF
0.0481%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0417%
Overall
0.00397%
64/1,614,094 alleles · ultra-rare
exomes 59/1,461,814 · genomes 5/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0668% | 1,496 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,501 |
| Admixed American | 0.005% | 20,007 |
| European (non-Finnish) | 0.00212% | 47,199 |
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
- SLC12A2
- Protein
- p.Phe372=
- Coding
- c.1116C>T
- MANE Select
- NM_001046
- Type
- single nucleotide variant
- Location
- chr5:128131134 (GRCh38)
- Gene constraint
- LOEUF 0.721 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.23 · 14 PDB
- Residue 372
- an α-helix; a binding site
Similar variants
- SLC12A2 p.Pro988Ser Pathogenic ★★ same type
- SLC12A2 p.Ala106Glu Uncertain significance ★★ ⚠ same type
- SLC12A2 p.Ala1189Val Uncertain significance ★★ ⚠ same type
- SLC12A2 p.Ala147Thr Uncertain significance ★★ ⚠ same type
- SLC12A2 p.Ala377Thr Uncertain significance ★★ ⚠ same type
- SLC12A2 p.Ala867Thr Uncertain significance ★★ ⚠ same type
- SLC12A2 p.Arg1148Gln Uncertain significance ★★ ⚠ same type
- SLC12A2 p.Arg294His Uncertain significance ★★ ⚠ 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/slc12a2-p-phe372 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown