CXADR p.Pro333=
c.999G>A · VCV4236397
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.189 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -3.4 |
| Overall | ||
| CADD | 0.754 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,868 alleles
Filtering AF
0.0005%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000868%
14/1,613,030 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,868 |
| Admixed American | 0.00167% | 59,976 |
| South Asian | 0.0011% | 91,038 |
| European (non-Finnish) | 0.000932% | 107,259 |
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
- CXADR
- Protein
- p.Pro333=
- Coding
- c.999G>A
- MANE Select
- NM_001338
- Type
- single nucleotide variant
- Location
- chr21:17565593 (GRCh38)
- Gene constraint
- LOEUF 0.751 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.51 · 23 PDB
- Residue 333
- the 'disordered' region
Similar variants
- CXADR p.Thr193= Benign ★★ same type
- CXADR p.Ala144Val Uncertain significance ★ ⚠ same type
- CXADR p.Arg217Lys Uncertain significance ★ ⚠ same type
- CXADR p.Arg226Pro Uncertain significance ★ ⚠ same type
- CXADR p.Arg264Cys Uncertain significance ★ ⚠ same type
- CXADR p.Arg287Cys Uncertain significance ★ ⚠ same type
- CXADR p.Arg328His Uncertain significance ★ ⚠ same type
- CXADR p.Arg90Gln 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/cxadr-p-pro333 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown