SLC19A1 p.Phe400=
c.1200C>T · rs149270420 · VCV729425
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.301 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.42 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -3.8 | GERP -3.5 |
| Overall | ||
| CADD | 2.648 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,060 alleles
Filtering AF
0.0239%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0229%
Overall
0.0221%
357/1,613,682 alleles · ultra-rare
exomes 332/1,461,318 · genomes 25/152,364 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,030 |
| Ashkenazi Jewishnot grpmax-eligible | 0.027% | 3,701 |
| European (non-Finnish) | 0.0264% | 3,794 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,807 |
| Admixed American | 0.02% | 5,003 |
| African / African-American | 0.00666% | 15,014 |
| South Asian | 0.00549% | 18,216 |
| East Asian | 0.00223% | 44,884 |
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.Phe400=
- Coding
- c.1200C>T
- MANE Select
- NM_194255
- dbSNP
- rs149270420
- Type
- single nucleotide variant
- Location
- chr21:45525910 (GRCh38)
- Gene constraint
- LOEUF 1.585 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.30 · 19 PDB
- Residue 400
- an α-helix; a binding site
Similar variants
- 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
- COL18A1 p.Arg1183His 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-phe400 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown