WRAP53 p.Thr424=
c.1272C>T · rs367678596 · VCV1117239
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0658%, 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 -12 | GERP -5.1 |
| Overall | ||
| CADD | 0.201 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0658%
Middle Eastern · 4/6,076 alleles
Filtering AF
0.0224%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0135%
Overall
0.0018%
29/1,613,712 alleles · ultra-rare
exomes 28/1,461,578 · genomes 1/152,134 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0658% | 1,519 |
| Admixed American | 0.0133% | 7,500 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| African / African-American | 0.00401% | 24,965 |
| East Asian | 0.00223% | 44,890 |
| South Asian | 0.0011% | 91,090 |
| European (non-Finnish) | 0.000763% | 131,115 |
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.Thr424=
- Coding
- c.1272C>T
- MANE Select
- NM_001143992
- dbSNP
- rs367678596
- Type
- single nucleotide variant
- Location
- chr17:7702996 (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 424
- 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-thr424 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown