SLC19A1 p.Ile414=
c.1242C>A · rs57725551 · VCV777643
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.31%, sas)
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 4.1 | GERP -3.5, phastCons 1 |
| Overall | ||
| CADD | 4.414 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.31%
South Asian · 2,101/91,082 alleles
Filtering AF
2.22%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.19%
Overall
0.305%
4,922/1,613,618 alleles · low-frequency
exomes 3,880/1,461,236 · genomes 1,042/152,382 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 2.31% | 43 |
| African / African-American | 2.11% | 47 |
| Middle Eastern | 0.512% | 195 |
| Remaining individualsnot grpmax-eligible | 0.386% | 259 |
| Admixed American | 0.208% | 480 |
| East Asian | 0.201% | 499 |
| European (non-Finnish) | 0.0619% | 1,616 |
| Finnishnot grpmax-eligible | 0.0268% | 3,734 |
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.Ile414=
- Coding
- c.1242C>A
- MANE Select
- NM_194255
- dbSNP
- rs57725551
- Type
- single nucleotide variant
- Location
- chr21:45525868 (GRCh38)
- Gene constraint
- LOEUF 1.585 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.30 · 19 PDB
- Residue 414
- an α-helix; the 'required for substrate-binding' region
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-ile414 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown