S1PR2 p.Pro321=
c.963G>A · rs748108934 · VCV2973543
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0118%, amr)
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 -20 | GERP -11 |
| Overall | ||
| CADD | 0.192 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0118%
Admixed American · 7/59,350 alleles
Filtering AF
0.00549%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00384%
Overall
0.00125%
20/1,603,132 alleles · ultra-rare
exomes 19/1,450,916 · genomes 1/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0118% | 8,479 |
| South Asian | 0.00111% | 89,938 |
| European (non-Finnish) | 0.00102% | 97,897 |
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
- S1PR2
- Protein
- p.Pro321=
- Coding
- c.963G>A
- MANE Select
- NM_004230
- dbSNP
- rs748108934
- Type
- single nucleotide variant
- Location
- chr19:10223943 (GRCh38)
- Gene constraint
- LOEUF 0.834 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 82.73 · 2 PDB
Similar variants
- S1PR2 p.Ala36Val Uncertain significance ★★ ⚠ same type
- S1PR2 p.Ala77Thr Uncertain significance ★★ ⚠ same type
- S1PR2 p.Ala77Val Uncertain significance ★★ ⚠ same type
- S1PR2 p.Arg211His Uncertain significance ★★ ⚠ same type
- S1PR2 p.Arg217His Uncertain significance ★★ ⚠ same type
- S1PR2 p.Arg293Trp Uncertain significance ★★ ⚠ same type
- S1PR2 p.Arg297Trp Uncertain significance ★★ ⚠ same type
- S1PR2 p.Arg315Gln 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/s1pr2-p-pro321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown