LRP2 p.Asp1111=
c.3333C>T · rs372322747 · VCV1577819
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.151%, sas)
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 -1.4 | GERP -3.6 |
| Overall | ||
| CADD | 0.293 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.151%
South Asian · 138/91,092 alleles
Filtering AF
0.131%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.123%
Overall
0.0137%
221/1,614,254 alleles · rare
exomes 202/1,461,892 · genomes 19/152,362 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.151% | 660 |
| Finnishnot grpmax-eligible | 0.0625% | 1,601 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,930 |
| European (non-Finnish) | 0.00305% | 32,779 |
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.Asp1111=
- Coding
- c.3333C>T
- MANE Select
- NM_004525
- dbSNP
- rs372322747
- Type
- single nucleotide variant
- Location
- chr2:169244790 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 1111
- the ldl-receptor class a 10 domain; a β-strand
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-asp1111 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown