SLC19A1 p.His569=
c.1707T>C · rs140055382 · VCV751025
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00966%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.86 | GERP -1.2, phastCons 0.009 |
| Overall | ||
| CADD | 0.942 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00966%
European (non-Finnish) · 114/1,180,026 alleles
Filtering AF
0.00817%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00761%
Overall
0.00787%
127/1,613,676 alleles · very rare
exomes 117/1,461,516 · genomes 10/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00966% | 10,351 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,617 |
| Finnishnot grpmax-eligible | 0.00628% | 15,932 |
| Admixed American | 0.005% | 19,999 |
| African / African-American | 0.00267% | 37,453 |
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
- SLC19A1
- Protein
- p.His569=
- Coding
- c.1707T>C
- MANE Select
- NM_194255
- dbSNP
- rs140055382
- Type
- single nucleotide variant
- Location
- chr21:45515727 (GRCh38)
- Gene constraint
- LOEUF 1.585 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.30 · 19 PDB
Similar variants
- SLC19A1 p.His569Tyr Uncertain significance ★ ⚠ same residue
- COL18A1 p.Arg1081Ter Pathogenic/Likely pathogenic ★★ same type
- COL18A1 p.Arg915Ter Pathogenic/Likely pathogenic ★★ same type
- RFC1 p.Arg383Ter Pathogenic/Likely pathogenic ★★ same type
- COL18A1 c.*30G>A Uncertain significance ★★ same type
- COL18A1 p.Ala1089Thr Uncertain significance ★★ ⚠ same type
- COL18A1 p.Ala1254Val Uncertain significance ★★ ⚠ same type
- COL18A1 p.Arg1081Gln 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/slc19a1-p-his569 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown