LRP2 p.Ser276=
c.828G>A · rs146048301 · VCV719333
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0657%, mid)
Conditions
1
Donnai-Barrow syndrome
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 0.36 | GERP -3.8, phastCons 0.58 |
| Overall | ||
| CADD | 4.481 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0657%
Middle Eastern · 4/6,084 alleles
Filtering AF
0.0483%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0469%
Overall
0.0416%
671/1,613,904 alleles · ultra-rare
exomes 646/1,461,844 · genomes 25/152,060 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0657% | 1,521 |
| Remaining individualsnot grpmax-eligible | 0.0576% | 1,736 |
| European (non-Finnish) | 0.0517% | 1,934 |
| South Asian | 0.011% | 9,108 |
| Admixed American | 0.00834% | 11,998 |
| African / African-American | 0.00534% | 18,716 |
| East Asian | 0.00223% | 44,890 |
| Finnishnot grpmax-eligible | 0.00156% | 63,994 |
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.Ser276=
- Coding
- c.828G>A
- MANE Select
- NM_004525
- dbSNP
- rs146048301
- Type
- single nucleotide variant
- Location
- chr2:169290939 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 276
- the ldl-receptor class a 7 domain
Similar variants
- LRP2 p.Ser276Leu 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-ser276 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown