SLC19A2 p.Ala460=
c.1380C>T · rs151078749 · VCV724315
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.04%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.23 | acceptor loss · deltas |
|---|---|---|
| Pangolin | Δ0.40 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -4 |
| Overall | ||
| CADD | 0.133 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.04%
African / African-American · 30/74,974 alleles
Filtering AF
0.0288%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0249%
Overall
0.00223%
36/1,613,862 alleles · ultra-rare
exomes 17/1,461,746 · genomes 19/152,116 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.04% | 2,499 |
| Admixed American | 0.00333% | 29,995 |
| South Asian | 0.0022% | 45,531 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,496 |
| European (non-Finnish) | 8.48e-05% | 1,179,917 |
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.Ala460=
- Coding
- c.1380C>T
- MANE Select
- NM_006996
- dbSNP
- rs151078749
- Type
- single nucleotide variant
- Location
- chr1:169465963 (GRCh38)
- Gene constraint
- LOEUF 0.852 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.99 · 2 PDB
- Residue 460
- an α-helix
Similar variants
- 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
- SLC19A2 p.Gly172Asp 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-ala460 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown