SLC45A2 p.Pro419=
c.1257G>A · rs989974325 · VCV1118893
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00593%, 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 -10 | GERP -5.2 |
| Overall | ||
| CADD | 3.012 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00593%
European (non-Finnish) · 70/1,180,032 alleles
Filtering AF
0.00478%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00439%
Overall
0.00465%
75/1,614,064 alleles · very rare
exomes 70/1,461,890 · genomes 5/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00593% | 16,858 |
| African / African-American | 0.004% | 24,977 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| Admixed American | 0.00167% | 60,008 |
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
- SLC45A2
- Protein
- p.Pro419=
- Coding
- c.1257G>A
- MANE Select
- NM_016180
- dbSNP
- rs989974325
- Type
- single nucleotide variant
- Location
- chr5:33947274 (GRCh38)
- Gene constraint
- LOEUF 1.022 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.96
Similar variants
- SLC45A2 p.Pro419Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
- SLC45A2 p.Pro419Thr Uncertain significance ★★ ⚠ same residue
- SLC45A2 c.1156+1G>C Pathogenic/Likely pathogenic ★★ same type
- SLC45A2 c.386-1G>A Pathogenic ★★ same type
- SLC45A2 p.Ala486Thr Pathogenic/Likely pathogenic ★★ same type
- SLC45A2 p.Ala511Glu Pathogenic ★★ same type
- SLC45A2 p.Arg102Gln Pathogenic/Likely pathogenic ★★ same type
- SLC45A2 p.Asn122Ser 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/slc45a2-p-pro419 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown