LRP2 p.Asp749=
c.2247C>T · rs562363182 · VCV1558710
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0692%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.8 | GERP -2.5, phastCons 1 |
| Overall | ||
| CADD | 7.849 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0692%
East Asian · 31/44,830 alleles
Filtering AF
0.05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0435%
Overall
0.00632%
102/1,613,188 alleles · ultra-rare
exomes 91/1,461,234 · genomes 11/151,954 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0692% | 1,446 |
| Middle Eastern | 0.0165% | 6,052 |
| Admixed American | 0.01% | 9,976 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,493 |
| South Asian | 0.00549% | 18,213 |
| European (non-Finnish) | 0.00441% | 22,684 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,566 |
| African / African-American | 0.00134% | 74,902 |
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.Asp749=
- Coding
- c.2247C>T
- MANE Select
- NM_004525
- dbSNP
- rs562363182
- Type
- single nucleotide variant
- Location
- chr2:169270977 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 749
- 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-asp749 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown