SLC6A3 p.Pro554=
c.1662C>T · rs758772852 · VCV697722
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00891%, eas)
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 -6.9 | GERP -3.4 |
| Overall | ||
| CADD | 2.076 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00891%
East Asian · 4/44,884 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.00105%
17/1,614,018 alleles · very rare
exomes 17/1,461,694 · genomes 0/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00891% | 11,221 |
| Admixed American | 0.00167% | 60,026 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,502 |
| European (non-Finnish) | 0.000932% | 107,274 |
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
- SLC6A3
- Protein
- p.Pro554=
- Coding
- c.1662C>T
- MANE Select
- NM_001044
- dbSNP
- rs758772852
- Type
- single nucleotide variant
- Location
- chr5:1403027 (GRCh38)
- Gene constraint
- LOEUF 0.393 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.58 · 12 PDB
Similar variants
- SLC6A3 c.1269+1G>A Pathogenic ★★ same type
- SLC6A3 p.Ala308Val Uncertain significance ★★ ⚠ same type
- SLC6A3 p.Ala346Val Uncertain significance ★★ ⚠ same type
- SLC6A3 p.Ala565Ser Uncertain significance ★★ ⚠ same type
- SLC6A3 p.Ala57Val Uncertain significance ★★ ⚠ same type
- SLC6A3 p.Arg304Gln Uncertain significance ★★ ⚠ same type
- SLC6A3 p.Arg51Gln Uncertain significance ★★ ⚠ same type
- SLC6A3 p.Arg588Gln 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/slc6a3-p-pro554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown