Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 11 submitters
gnomAD v4.1
Common
common (popmax 86.2%, eas) — too common for a highly-penetrant pathogenic allele
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 1.7 | GERP -1.6, phastCons 1 |
| Overall | ||
| CADD | 5.813 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
86.2%
East Asian · 38,690/44,862 alleles
Filtering AF
85.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 85.2%
Overall
64.7%
1,043,351/1,613,364 alleles · common
exomes 949,919/1,461,358 · genomes 93,432/152,006 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 86.2% | 1 |
| Middle Eastern | 71.9% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 70.6% | 1 |
| Amishnot grpmax-eligible | 68.6% | 1 |
| Finnishnot grpmax-eligible | 67.1% | 1 |
| European (non-Finnish) | 66.1% | 2 |
| Remaining individualsnot grpmax-eligible | 65.4% | 2 |
| African / African-American | 52.2% | 2 |
| South Asian | 50.7% | 2 |
| Admixed American | 50.3% | 2 |
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.Val675=
- Coding
- c.2025C>T
- MANE Select
- NM_004525
- dbSNP
- rs830994
- Type
- single nucleotide variant
- Location
- chr2:169273018 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 675
- a β-strand
Similar variants
- LRP2 p.Val675Ala Benign/Likely benign ★★ 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-val675 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown