LRP2 p.Pro325=
c.975G>A · rs368492082 · VCV1648446
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0379%, eas)
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 -0.89 | GERP -2.8 |
| Overall | ||
| CADD | 2.997 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0379%
East Asian · 17/44,882 alleles
Filtering AF
0.0241%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0197%
Overall
0.00998%
161/1,613,968 alleles · ultra-rare
exomes 143/1,461,818 · genomes 18/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0379% | 2,640 |
| Admixed American | 0.0233% | 4,286 |
| African / African-American | 0.016% | 6,242 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,413 |
| European (non-Finnish) | 0.00915% | 10,926 |
| South Asian | 0.00439% | 22,772 |
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.Pro325=
- Coding
- c.975G>A
- MANE Select
- NM_004525
- dbSNP
- rs368492082
- Type
- single nucleotide variant
- Location
- chr2:169289093 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Similar variants
- LRP2 p.Pro325Leu Uncertain significance ★★ same residue
- LRP2 p.Pro325Gln 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-pro325 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown