LRP2 p.Pro662=
c.1986G>A · rs779851629 · VCV2960421
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -7.2 | GERP -4.1 |
| Overall | ||
| CADD | 0.338 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,074 alleles
Filtering AF
0.00196%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00168%
Overall
0.00217%
35/1,613,434 alleles · ultra-rare
exomes 32/1,461,306 · genomes 3/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,074 |
| European (non-Finnish) | 0.00271% | 36,864 |
| African / African-American | 0.00134% | 74,874 |
| South Asian | 0.0011% | 91,086 |
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.Pro662=
- Coding
- c.1986G>A
- MANE Select
- NM_004525
- dbSNP
- rs779851629
- Type
- single nucleotide variant
- Location
- chr2:169273057 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 662
- an α-helix
Similar variants
- LRP2 p.Pro662Leu 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-pro662 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown