SLC1A2 p.Pro223=
c.669G>A · rs372812420 · VCV1627634
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, 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 -10 | GERP -3.9 |
| Overall | ||
| CADD | 0.099 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/60,006 alleles
Filtering AF
0.009%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00681%
Overall
0.00459%
74/1,613,952 alleles · ultra-rare
exomes 67/1,461,776 · genomes 7/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 6,001 |
| European (non-Finnish) | 0.00517% | 19,344 |
| African / African-American | 0.00267% | 37,451 |
| East Asian | 0.00223% | 44,894 |
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
- SLC1A2
- Protein
- p.Pro223=
- Coding
- c.669G>A
- MANE Select
- NM_004171
- dbSNP
- rs372812420
- Type
- single nucleotide variant
- Location
- chr11:35306135 (GRCh38)
- Gene constraint
- LOEUF 0.569 · pLI 0.84 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.64 · 7 PDB
Similar variants
- SLC1A2 p.Pro223Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- SLC1A2 p.Pro223Leu Uncertain significance ★ ⚠ same residue
- SLC1A2 p.Pro289Arg Pathogenic/Likely pathogenic ★★ same type
- SLC1A2 c.562-2A>G Uncertain significance ★★ same type
- SLC1A2 p.Ala210Thr Uncertain significance ★★ ⚠ same type
- SLC1A2 p.Ala293Thr Uncertain significance ★★ ⚠ same type
- SLC1A2 p.Ala349Thr Uncertain significance ★★ ⚠ same type
- SLC1A2 p.Ala349Val 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/slc1a2-p-pro223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown