LRP2 p.Ser1695=
c.5085G>A · rs145384264 · VCV129527
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.85%, 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 -7.3 | GERP -3.5 |
| Overall | ||
| CADD | 0.198 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.85%
European (non-Finnish) · 21,886/1,179,982 alleles
Filtering AF
1.83%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.83%
Overall
1.5%
24,214/1,614,094 alleles · low-frequency
exomes 22,748/1,461,846 · genomes 1,466/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.85% | 54 |
| Remaining individualsnot grpmax-eligible | 1.27% | 79 |
| Admixed American | 0.646% | 155 |
| Finnishnot grpmax-eligible | 0.636% | 157 |
| South Asian | 0.5% | 200 |
| African / African-American | 0.276% | 362 |
| Ashkenazi Jewishnot grpmax-eligible | 0.216% | 463 |
| Middle Eastern | 0.214% | 466 |
| East Asian | 0.00446% | 22,438 |
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.Ser1695=
- Coding
- c.5085G>A
- MANE Select
- NM_004525
- dbSNP
- rs145384264
- Type
- single nucleotide variant
- Location
- chr2:169233424 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 1695
- an α-helix
Similar variants
- 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
- LRP2 p.Arg3184Ter 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-ser1695 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown