SLC40A1 p.Pro282=
c.846T>C · rs763703768 · VCV2897466
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
hemochromatosis type 4
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 -1.4 | GERP -5.1 |
| Overall | ||
| CADD | 3.531 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,878 alleles
Overall
0.000124%
2/1,612,272 alleles · very rare
exomes 2/1,459,940 · genomes 0/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,878 |
| European (non-Finnish) | 8.48e-05% | 1,179,382 |
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
- SLC40A1
- Protein
- p.Pro282=
- Coding
- c.846T>C
- MANE Select
- NM_014585
- dbSNP
- rs763703768
- Type
- single nucleotide variant
- Location
- chr2:189564140 (GRCh38)
- Gene constraint
- LOEUF 0.445 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.26 · 8 PDB
Similar variants
- SLC40A1 p.Arg178Gln Pathogenic/Likely pathogenic ★★ same condition
- SLC40A1 p.Arg88Gly Pathogenic/Likely pathogenic ★★ same condition
- SLC40A1 p.Arg88Thr Pathogenic/Likely pathogenic ★★ same condition
- SLC40A1 p.Asn144Asp Pathogenic ★★ ⚠ same condition
- SLC40A1 p.Asp157Gly Likely pathogenic ★★ same condition
- SLC40A1 p.Cys326Tyr Pathogenic ★★ ⚠ same condition
- SLC40A1 p.Gly204Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
- SLC40A1 p.Gly490Asp Pathogenic ★★ same condition
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/slc40a1-p-pro282 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown