LRP2 p.Pro4379=
c.13137C>A · rs140160600 · VCV1551517
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0107%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.29 | acceptor loss, 9 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.58 | GERP -2.4 |
| Overall | ||
| CADD | 0.566 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0107%
African / African-American · 8/74,916 alleles
Filtering AF
0.00528%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00381%
Overall
0.000991%
16/1,613,808 alleles · ultra-rare
exomes 11/1,461,616 · genomes 5/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0107% | 9,365 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| East Asian | 0.00223% | 44,884 |
| European (non-Finnish) | 0.000339% | 294,961 |
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.Pro4379=
- Coding
- c.13137C>A
- MANE Select
- NM_004525
- dbSNP
- rs140160600
- Type
- single nucleotide variant
- Location
- chr2:169140517 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 4379
- an α-helix; the egf-like 6 domain
Similar variants
- LRP2 p.Pro4379Ser Uncertain significance ★★ ⚠ same residue
- LRP2 c.12019+1G>A Likely pathogenic ★★ same type
- LRP2 c.2639+1G>A Pathogenic/Likely pathogenic ★★ same type
- LRP2 c.3667+1G>A Pathogenic/Likely pathogenic ★★ same type
- LRP2 c.8452+1G>A Pathogenic ★★ same type
- LRP2 p.Arg1953Ter Pathogenic/Likely pathogenic ★★ same type
- LRP2 p.Arg2095Ter Pathogenic/Likely pathogenic ★★ same type
- LRP2 p.Arg2225Ter Pathogenic/Likely pathogenic ★★ same type
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-pro4379 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown