WRAP53 p.Asp422=
c.1266C>T · rs376456857 · VCV2887258
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00935%, 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 0.41 | GERP -1.9, phastCons 0.97 |
| Overall | ||
| CADD | 4.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00935%
African / African-American · 7/74,882 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00309%
Overall
0.00062%
10/1,613,754 alleles · very rare
exomes 4/1,461,626 · genomes 6/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00935% | 10,697 |
| Admixed American | 0.005% | 20,001 |
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.Asp422=
- Coding
- c.1266C>T
- MANE Select
- NM_001143992
- dbSNP
- rs376456857
- Type
- single nucleotide variant
- Location
- chr17:7702844 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.96 · 7 PDB
Similar variants
- WRAP53 p.Asp422Asn 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-asp422 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown