LRP2 p.Ser3774=
c.11322G>A · rs141727314 · VCV332093
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0412%, nfe)
Conditions
1
Donnai-Barrow syndrome
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 0.29 | GERP -3.3, phastCons 0.14 |
| Overall | ||
| CADD | 1.487 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0412%
European (non-Finnish) · 486/1,180,034 alleles
Filtering AF
0.0381%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0369%
Overall
0.034%
548/1,614,054 alleles · ultra-rare
exomes 500/1,461,878 · genomes 48/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0412% | 2,428 |
| Middle Eastern | 0.0329% | 3,042 |
| South Asian | 0.0285% | 3,503 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,807 |
| Admixed American | 0.0183% | 5,455 |
| African / African-American | 0.00935% | 10,700 |
| East Asian | 0.00668% | 14,967 |
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.Ser3774=
- Coding
- c.11322G>A
- MANE Select
- NM_004525
- dbSNP
- rs141727314
- Type
- single nucleotide variant
- Location
- chr2:169170609 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 3774
- an α-helix; the ldl-receptor class a 32 domain
Similar variants
- LRP2 p.Ser3774Leu Uncertain significance ★ same residue
- LRP2 c.12019+1G>A Likely pathogenic ★★ same condition
- LRP2 c.2639+1G>A Pathogenic/Likely pathogenic ★★ same condition
- LRP2 c.3667+1G>A Pathogenic/Likely pathogenic ★★ same condition
- LRP2 c.8452+1G>A Pathogenic ★★ same condition
- LRP2 p.Arg1953Ter Pathogenic/Likely pathogenic ★★ same condition
- LRP2 p.Arg2225Ter Pathogenic/Likely pathogenic ★★ same condition
- LRP2 p.Arg278Ter Pathogenic/Likely pathogenic ★★ same condition
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-ser3774 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown