SLC22A4 p.Pro46=
c.138G>A · rs767014071 · VCV805280
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -4.9 | GERP -5.5 |
| Overall | ||
| CADD | 1.269 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00307%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00275%
Overall
0.00335%
54/1,613,648 alleles · ultra-rare
exomes 48/1,461,474 · genomes 6/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Admixed American | 0.00667% | 15,003 |
| European (non-Finnish) | 0.00398% | 25,107 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,238 |
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
- SLC22A4
- Protein
- p.Pro46=
- Coding
- c.138G>A
- MANE Select
- NM_003059
- dbSNP
- rs767014071
- Type
- single nucleotide variant
- Location
- chr5:132294754 (GRCh38)
- Gene constraint
- LOEUF 0.982 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.07
Similar variants
- SLC22A4 c.393+1G>A Uncertain significance ★★ same type
- SLC22A4 p.Ala61Thr Uncertain significance ★★ ⚠ same type
- SLC22A4 p.Arg70Pro Uncertain significance ★★ ⚠ same type
- SLC22A4 p.Gly15Arg Uncertain significance ★★ ⚠ same type
- SLC22A4 p.Gly96Arg Uncertain significance ★★ same type
- SLC22A4 c.1046+5G>A Benign ★★ same type
- SLC22A4 p.Cys113= Benign/Likely benign ★★ same type
- SLC22A4 p.Gly471= Benign ★★ 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/slc22a4-p-pro46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown