SLC12A2 p.Ser960=
c.2880C>T · rs780180222 · VCV2422119
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00168%, amr)
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 -0.9 | GERP -5.3 |
| Overall | ||
| CADD | 1.458 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00168%
Admixed American · 1/59,598 alleles
Filtering AF
0.000956%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000789%
Overall
0.00131%
21/1,608,392 alleles · very rare
exomes 20/1,456,480 · genomes 1/151,912 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00168% | 59,598 |
| European (non-Finnish) | 0.00153% | 65,382 |
| African / African-American | 0.00134% | 74,716 |
| South Asian | 0.00111% | 90,158 |
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.Ser960=
- Coding
- c.2880C>T
- MANE Select
- NM_001046
- dbSNP
- rs780180222
- Type
- single nucleotide variant
- Location
- chr5:128174617 (GRCh38)
- Gene constraint
- LOEUF 0.721 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.23 · 14 PDB
- Residue 960
- a UniProt-annotated variant site (in delmnes)
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-ser960 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown