IRF2BP2 p.Pro522=
c.1566G>A · rs144158289 · VCV1664759
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.073%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.1 | GERP -3.9 |
| Overall | ||
| CADD | 6.699 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.073%
European (non-Finnish) · 861/1,180,042 alleles
Filtering AF
0.0689%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0673%
Overall
0.0548%
885/1,614,082 alleles · ultra-rare
exomes 839/1,461,880 · genomes 46/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.073% | 1,371 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,249 |
| African / African-American | 0.00934% | 10,704 |
| Admixed American | 0.005% | 20,001 |
| Finnishnot grpmax-eligible | 0.00312% | 32,015 |
| South Asian | 0.0022% | 45,546 |
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
- IRF2BP2
- Protein
- p.Pro522=
- Coding
- c.1566G>A
- MANE Select
- NM_182972
- dbSNP
- rs144158289
- Type
- single nucleotide variant
- Location
- chr1:234607335 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI 0.41 (gnomAD)
- Structure
- AlphaFold pLDDT 56.84 · 3 PDB
- Residue 522
- the 'cys-rich' region
Similar variants
- IRF2BP2 p.Ala143Gly Uncertain significance ★★ ⚠ same type
- IRF2BP2 p.Ala209Gly Uncertain significance ★★ ⚠ same type
- IRF2BP2 p.Ala214Thr Uncertain significance ★★ ⚠ same type
- IRF2BP2 p.Ala246Val Uncertain significance ★★ ⚠ same type
- IRF2BP2 p.Ala254Thr Uncertain significance ★★ ⚠ same type
- IRF2BP2 p.Ala276Thr Uncertain significance ★★ ⚠ same type
- IRF2BP2 p.Ala344Val Uncertain significance ★★ ⚠ same type
- IRF2BP2 p.Ala502Ser 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/irf2bp2-p-pro522 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown