Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Common
common (popmax 51.4%, amr) — too common for a highly-penetrant pathogenic allele
Conditions
1
Donnai-Barrow syndrome
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 0.77 | GERP -2.2, phastCons 0.95 |
| Overall | ||
| CADD | 10.57 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
51.4%
Admixed American · 30,808/59,948 alleles
Filtering AF
50.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 50.7%
Overall
28%
448,907/1,602,868 alleles · common
exomes 402,433/1,451,048 · genomes 46,474/151,820 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 51.4% | 2 |
| East Asian | 43.6% | 2 |
| Amishnot grpmax-eligible | 39.8% | 3 |
| African / African-American | 33.3% | 3 |
| South Asian | 32.9% | 3 |
| Remaining individualsnot grpmax-eligible | 28.5% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 26.8% | 4 |
| European (non-Finnish) | 25.8% | 4 |
| Middle Eastern | 22.5% | 4 |
| Finnishnot grpmax-eligible | 22.2% | 5 |
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.Asp213=
- Coding
- c.639C>T
- MANE Select
- NM_004525
- dbSNP
- rs2229266
- Type
- single nucleotide variant
- Location
- chr2:169294161 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 213
- the ldl-receptor class a 5 domain
Similar variants
- 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
- LRP2 p.Arg278Ter Pathogenic/Likely pathogenic ★★ same condition
- LRP2 p.Arg3184Ter 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-asp213 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown