LRP2 p.Asp2253=
c.6759T>C · rs35114151 · VCV129535
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 10.5%, afr) — 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 0.097 | GERP -1.9, phastCons 0.065 |
| Overall | ||
| CADD | 2.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
10.5%
African / African-American · 7,907/75,018 alleles
Filtering AF
10.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.3%
Overall
2.8%
45,124/1,614,166 alleles · common
exomes 37,832/1,461,880 · genomes 7,292/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 10.5% | 9 |
| South Asian | 7.53% | 13 |
| Ashkenazi Jewishnot grpmax-eligible | 6.56% | 15 |
| Finnishnot grpmax-eligible | 4.05% | 25 |
| Middle Eastern | 3.65% | 27 |
| Remaining individualsnot grpmax-eligible | 3.19% | 31 |
| East Asian | 2.79% | 36 |
| European (non-Finnish) | 1.83% | 55 |
| Admixed American | 1.18% | 84 |
| Amishnot grpmax-eligible | 0.11% | 912 |
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.Asp2253=
- Coding
- c.6759T>C
- MANE Select
- NM_004525
- dbSNP
- rs35114151
- Type
- single nucleotide variant
- Location
- chr2:169206961 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 2253
- a turn
Similar variants
- LRP2 p.Asp2253Ala Uncertain significance ★ ⚠ same residue
- LRP2 p.Asp2253Asn 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-asp2253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown