SLC19A2 p.Tyr378=
c.1134T>C · rs781443514 · VCV1988328
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0987%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>C here scores Δ0.30 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -3.9 |
| Overall | ||
| CADD | 2.362 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0987%
Middle Eastern · 6/6,080 alleles
Filtering AF
0.0429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0293%
Overall
0.00298%
48/1,612,652 alleles · ultra-rare
exomes 45/1,460,478 · genomes 3/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0987% | 1,013 |
| European (non-Finnish) | 0.00348% | 28,752 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,440 |
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
- SLC19A2
- Protein
- p.Tyr378=
- Coding
- c.1134T>C
- MANE Select
- NM_006996
- dbSNP
- rs781443514
- Type
- single nucleotide variant
- Location
- chr1:169468733 (GRCh38)
- Gene constraint
- LOEUF 0.852 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.99 · 2 PDB
- Residue 378
- an α-helix
Similar variants
- SLC19A2 p.Tyr378Ter Pathogenic ★ same residue
- SLC19A2 c.1223+1G>A Pathogenic ★★ same type
- SLC19A2 c.807+2T>G Likely pathogenic ★★ same type
- SLC19A2 p.Arg162Ter Pathogenic ★★ same type
- SLC19A2 p.Arg397Ter Pathogenic/Likely pathogenic ★★ same type
- SLC19A2 p.Gln233Ter Pathogenic ★★ same type
- SLC19A2 p.Glu66Ter Pathogenic ★★ same type
- SLC19A2 p.Gly105Glu Pathogenic/Likely pathogenic ★★ 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/slc19a2-p-tyr378 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown