SLC19A3 p.Trp59Ter
c.177G>A · rs2470575306 · VCV2840050
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 3 of 6 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.29 | loss · gain 0.01 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 38.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- SLC19A3
- Protein
- p.Trp59Ter
- Coding
- c.177G>A
- MANE Select
- NM_025243
- dbSNP
- rs2470575306
- Type
- single nucleotide variant
- Location
- chr2:227699538 (GRCh38)
- Gene constraint
- LOEUF 0.968 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.96 · 19 PDB
- Residue 59
- an α-helix
Disease context
biotin-responsive basal ganglia disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Thiamine-responsive encephalopathy (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent
Similar variants
- SLC19A3 p.Trp59Arg Uncertain significance ★★ ⚠ same residue
- SLC19A3 c.1172+1G>A Pathogenic/Likely pathogenic ★★ same condition
- SLC19A3 c.1172+2T>G Pathogenic ★★ same condition
- SLC19A3 c.1173-1G>A Pathogenic/Likely pathogenic ★★ same condition
- SLC19A3 c.151-1G>C Likely pathogenic ★★ same condition
- SLC19A3 c.980-14A>G Pathogenic/Likely pathogenic ★★ same condition
- SLC19A3 p.Gly23Val Pathogenic/Likely pathogenic ★★ same condition
- SLC19A3 p.Met1Leu Likely pathogenic ★★ same condition
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/slc19a3-p-trp59ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown