IRF2BPL p.Pro253=
c.759C>T · VCV3357870
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00545%, afr)
Conditions
1
IRF2BPL-related disorder
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 0.69 | GERP -1.1, phastCons 0.99 |
| Overall | ||
| CADD | 10.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00545%
African / African-American · 4/73,416 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00106%
Overall
0.000324%
5/1,543,016 alleles · very rare
exomes 3/1,390,810 · genomes 2/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00545% | 18,354 |
| Admixed American | 0.00196% | 50,970 |
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
- IRF2BPL
- Protein
- p.Pro253=
- Coding
- c.759C>T
- MANE Select
- NM_024496
- Type
- single nucleotide variant
- Location
- chr14:77027034 (GRCh38)
- Gene constraint
- LOEUF 0.544 · pLI 0.91 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.01 · 1 PDB
- Residue 253
- the 'disordered' region; a UniProt-annotated variant site (in nedamss); a UniProt-annotated variant site (in nedamss; loss of function)
Similar variants
- IRF2BPL p.Pro253His Uncertain significance ★ ⚠ same residue
- IRF2BPL p.Pro253Ser Likely benign ★ same residue
- IRF2BPL p.Gln122Ter Pathogenic/Likely pathogenic ★★ same condition
- IRF2BPL p.Glu172Ter Pathogenic/Likely pathogenic ★★ same condition
- IRF2BPL p.Arg391His Likely pathogenic ★ same condition
- IRF2BPL p.Gln249Ter Likely pathogenic ★ same condition
- IRF2BPL p.Phe420Ser Likely pathogenic ★ same condition
- IRF2BPL p.Pro372Ala Likely pathogenic ★ ⚠ same condition
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/irf2bpl-p-pro253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown