WRAP53 p.Pro459=
c.1377C>G · rs747113105 · VCV1120812
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.115%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -4.1, phastCons 0.001 |
| Overall | ||
| CADD | 5.42 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.115%
Middle Eastern · 7/6,062 alleles
Filtering AF
0.0542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0384%
Overall
0.00062%
10/1,614,082 alleles · rare
exomes 10/1,461,842 · genomes 0/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.115% | 866 |
| European (non-Finnish) | 0.000254% | 393,342 |
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
- WRAP53
- Protein
- p.Pro459=
- Coding
- c.1377C>G
- MANE Select
- NM_001143992
- dbSNP
- rs747113105
- Type
- single nucleotide variant
- Location
- chr17:7703101 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.96 · 7 PDB
- Residue 459
- a β-strand
Similar variants
- WRAP53 c.823-3C>T Uncertain significance ★★ same type
- WRAP53 p.Ala118Thr Uncertain significance ★★ ⚠ same type
- WRAP53 p.Arg265Gln Uncertain significance ★★ ⚠ same type
- WRAP53 p.Arg298Gln Uncertain significance ★★ ⚠ same type
- WRAP53 p.Arg298Gly Uncertain significance ★★ ⚠ same type
- WRAP53 p.Arg298Trp Uncertain significance ★★ same type
- WRAP53 p.Arg301Cys Uncertain significance ★★ ⚠ same type
- WRAP53 p.Arg307Gln 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/wrap53-p-pro459 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown