Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.5%, afr)
Conditions
1
Donnai-Barrow syndrome
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 -0.78 | GERP -3, phastCons 0.02 |
| Overall | ||
| CADD | 9.809 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.5%
African / African-American · 3,376/74,984 alleles
Filtering AF
4.38%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.32%
Overall
0.243%
3,920/1,613,880 alleles · low-frequency
exomes 1,941/1,461,642 · genomes 1,979/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.5% | 22 |
| Middle Eastern | 0.38% | 263 |
| Remaining individualsnot grpmax-eligible | 0.309% | 324 |
| Admixed American | 0.275% | 364 |
| South Asian | 0.128% | 778 |
| European (non-Finnish) | 0.0039% | 25,649 |
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
- LRP2
- Protein
- p.Pro2089=
- Coding
- c.6267G>A
- MANE Select
- NM_004525
- dbSNP
- rs2228169
- Type
- single nucleotide variant
- Location
- chr2:169211981 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Similar variants
- LRP2 p.Pro2089Leu Uncertain significance ★★ ⚠ same residue
- LRP2 p.Pro2089Ser Uncertain significance ★ ⚠ same residue
- LRP2 c.12019+1G>A Likely pathogenic ★★ same condition
- LRP2 c.2639+1G>A Pathogenic/Likely pathogenic ★★ same condition
- LRP2 c.3667+1G>A Pathogenic/Likely pathogenic ★★ same condition
- LRP2 c.8452+1G>A Pathogenic ★★ same condition
- LRP2 p.Arg1953Ter Pathogenic/Likely pathogenic ★★ same condition
- LRP2 p.Arg2225Ter Pathogenic/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/lrp2-p-pro2089 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown