SLC18A2 p.Pro387=
c.1161G>A · rs779480733 · VCV1970908
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00576%, sas)
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 0.2 | GERP -1.2, phastCons 0.96 |
| Overall | ||
| CADD | 15.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00576%
South Asian · 5/86,770 alleles
Filtering AF
0.00218%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00142%
Overall
0.000639%
10/1,564,478 alleles · very rare
exomes 8/1,412,384 · genomes 2/152,094 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00576% | 17,354 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00351% | 28,498 |
| European (non-Finnish) | 0.00035% | 285,540 |
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
- SLC18A2
- Protein
- p.Pro387=
- Coding
- c.1161G>A
- MANE Select
- NM_003054
- dbSNP
- rs779480733
- Type
- single nucleotide variant
- Location
- chr10:117267711 (GRCh38)
- Gene constraint
- LOEUF 0.68 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.27 · 32 PDB
- Residue 387
- an α-helix; a UniProt-annotated variant site (in pkdys2; strong decrease in serotonin transport)
Similar variants
- SLC18A2 p.Pro387Leu Pathogenic/Likely pathogenic ★★ same residue
- SLC18A2 c.834+6C>T Uncertain significance ★★ same type
- SLC18A2 p.Ala164Val Uncertain significance ★★ ⚠ same type
- SLC18A2 p.Ala425Val Uncertain significance ★★ ⚠ same type
- SLC18A2 p.Arg17Cys Uncertain significance ★★ ⚠ same type
- SLC18A2 p.Gly448Glu Uncertain significance ★★ ⚠ same type
- SLC18A2 p.Ile339Val Uncertain significance ★★ ⚠ same type
- SLC18A2 p.Leu260Val 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/slc18a2-p-pro387 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown