IREB2 p.Asp274=
c.822C>T · rs2051384573 · VCV2645611
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000593%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 9.805 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000593%
European (non-Finnish) · 7/1,179,750 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000434%
7/1,613,626 alleles · very rare
exomes 7/1,461,326 · genomes 0/152,300 · joint denominator
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
- IREB2
- Protein
- p.Asp274=
- Coding
- c.822C>T
- MANE Select
- NM_004136
- dbSNP
- rs2051384573
- Type
- single nucleotide variant
- Location
- chr15:78471863 (GRCh38)
- Gene constraint
- LOEUF 0.389 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.11 · 1 PDB
Similar variants
- IREB2 p.Ala534Thr Uncertain significance ★★ ⚠ same type
- IREB2 p.Arg697Trp Uncertain significance ★★ ⚠ same type
- IREB2 p.Asn925Thr Uncertain significance ★★ ⚠ same type
- IREB2 p.Cys53Tyr Uncertain significance ★★ same type
- IREB2 p.Glu917Lys Uncertain significance ★★ ⚠ same type
- IREB2 p.Gly184Asp Uncertain significance ★★ ⚠ same type
- IREB2 p.Gly656Ser Uncertain significance ★★ ⚠ same type
- IREB2 p.His22Leu 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/ireb2-p-asp274 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown