WRAP53 p.Glu46=
c.138A>G · rs142177444 · VCV1640312
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0334%, afr)
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 -0.17 | GERP -5.2, phastCons 0.023 |
| Overall | ||
| CADD | 2.053 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0334%
African / African-American · 25/74,900 alleles
Filtering AF
0.0231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0198%
Overall
0.00167%
27/1,613,996 alleles · ultra-rare
exomes 11/1,461,894 · genomes 16/152,102 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0334% | 2,996 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
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.Glu46=
- Coding
- c.138A>G
- MANE Select
- NM_001143992
- dbSNP
- rs142177444
- Type
- single nucleotide variant
- Location
- chr17:7688786 (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 46
- the 'disordered' region
Similar variants
- WRAP53 p.Glu46Gln Uncertain significance ★ ⚠ same residue
- 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
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-glu46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown