IRF2BP2 p.Pro229=
c.687C>T · rs1251107516 · VCV1964248
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00456%, afr)
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 0.22 | GERP -2.1, phastCons 0.006 |
| Overall | ||
| CADD | 7.336 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00456%
African / African-American · 3/65,806 alleles
Filtering AF
0.00121%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000636%
Overall
0.000429%
6/1,399,048 alleles · very rare
exomes 5/1,247,022 · genomes 1/152,026 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00456% | 21,935 |
| European (non-Finnish) | 0.000276% | 361,925 |
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.Pro229=
- Coding
- c.687C>T
- MANE Select
- NM_182972
- dbSNP
- rs1251107516
- Type
- single nucleotide variant
- Location
- chr1:234608808 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI 0.41 (gnomAD)
- Structure
- AlphaFold pLDDT 56.84 · 3 PDB
- Residue 229
- the 'disordered' region
Similar variants
- IRF2BP2 p.Pro229Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro229 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown