WRAP53 p.Ser243=
c.729C>A · rs570343418 · VCV437303
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0484%, sas)
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 1.8 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 13.55 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0484%
South Asian · 44/91,002 alleles
Filtering AF
0.0369%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.033%
Overall
0.00317%
51/1,610,296 alleles · ultra-rare
exomes 49/1,458,042 · genomes 2/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0484% | 2,068 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,189 |
| European (non-Finnish) | 0.000425% | 235,338 |
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.Ser243=
- Coding
- c.729C>A
- MANE Select
- NM_001143992
- dbSNP
- rs570343418
- Type
- single nucleotide variant
- Location
- chr17:7700827 (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.Ser243Phe 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-ser243 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown