LRP2 p.Ile877=
c.2631C>T · rs139833815 · VCV1981708
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00401%, afr)
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 -0.21 | GERP -4.1, phastCons 0.006 |
| Overall | ||
| CADD | 0.491 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00401%
African / African-American · 3/74,834 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.00093%
15/1,612,500 alleles · very rare
exomes 12/1,460,430 · genomes 3/152,070 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,945 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,546 |
| South Asian | 0.0011% | 91,030 |
| European (non-Finnish) | 0.000848% | 117,902 |
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.Ile877=
- Coding
- c.2631C>T
- MANE Select
- NM_004525
- dbSNP
- rs139833815
- Type
- single nucleotide variant
- Location
- chr2:169257132 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 877
- a β-strand
Similar variants
- 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
- LRP2 p.Arg233Ter 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-ile877 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown