IRF2BPL p.Ser31Pro
c.91T>C · VCV3906582
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.8787 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.8787 | likely pathogenic |
|---|---|---|
| REVEL | 0.278 | benign-leaning |
| SaProt | LLR -12.16 | damaging |
| ⇒ AlphaMissense and SaProt call this damaging; REVEL does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.3 | GERP 0.18, phastCons 1 |
| Regional constraint | o/e 1.13 | unconstrained · MANE · 2,140 bp · p 2.6e-05 · regional, not allelic |
| Overall | ||
| CADD | 28.1 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- IRF2BPL
- Protein
- p.Ser31Pro
- Coding
- c.91T>C
- MANE Select
- NM_024496
- Type
- single nucleotide variant
- Location
- chr14:77027702 (GRCh38)
- Gene constraint
- LOEUF 0.544 · pLI 0.91 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.01 · 1 PDB
Similar variants
- IRF2BPL p.Arg188Ter Pathogenic/Likely pathogenic ★★ same type
- IRF2BPL p.Gln117Ter Likely pathogenic ★★ same type
- IRF2BPL p.Gln119Ter Likely pathogenic ★★ same type
- IRF2BPL p.Gln120Ter Pathogenic/Likely pathogenic ★★ same type
- IRF2BPL p.Gln121Ter Pathogenic/Likely pathogenic ★★ same type
- IRF2BPL p.Gln122Ter Pathogenic/Likely pathogenic ★★ same type
- IRF2BPL p.Gln167Ter Pathogenic/Likely pathogenic ★★ same type
- IRF2BPL p.Gln497Ter Pathogenic/Likely pathogenic ★★ 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/irf2bpl-p-ser31pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown