LRP2 p.Asp2914=
c.8742T>C · rs754129832 · VCV2970979
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>C here scores Δ0.22 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.92 | GERP -1.9, phastCons 0.057 |
| Overall | ||
| CADD | 1.079 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
South Asian · 30/91,086 alleles
Filtering AF
0.0237%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0205%
Overall
0.00198%
32/1,614,164 alleles · ultra-rare
exomes 32/1,461,866 · genomes 0/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0329% | 3,036 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| European (non-Finnish) | 8.47e-05% | 1,180,011 |
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.Asp2914=
- Coding
- c.8742T>C
- MANE Select
- NM_004525
- dbSNP
- rs754129832
- Type
- single nucleotide variant
- Location
- chr2:169193849 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 2914
- the ldl-receptor class a 21 domain
Similar variants
- LRP2 p.Asp2914Glu 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-asp2914 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown