Is LRP5 p.Pro848= (c.2544G>A) pathogenic?

LRP5 p.Pro848= (c.2544G>A) is classified Benign/Likely benign in LRP5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Rare (popmax 0.295%, afr); Associated with Bone mineral density quantitative trait locus 1.

What condition is associated with LRP5 p.Pro848= (c.2544G>A)?

LRP5 p.Pro848= (c.2544G>A) is associated with Bone mineral density quantitative trait locus 1, osteoporosis, exudative vitreoretinopathy 1 (ClinVar).

How common is LRP5 p.Pro848= (c.2544G>A) in the general population?

LRP5 p.Pro848= (c.2544G>A) is rare (popmax 0.295%, afr) (gnomAD).

LRP5 p.Pro848=

c.2544G>A · rs148271293 · VCV707894

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.295%, afr)

Conditions

Bone mineral density quantitative trait locus 1

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 -1.2	GERP -3.1
Overall
CADD	7.144	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.295% African / African-American · 221/75,036 alleles

Filtering AF 0.263% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.25%

Overall 0.0147% 238/1,613,714 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.295%	340
Admixed American	0.0133%	7,502
Remaining individualsnot grpmax-eligible	0.0112%	8,928
European (non-Finnish)	0.000169%	589,981

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: LRP5
Protein: p.Pro848=
Coding: c.2544G>A
MANE Select: NM_002335
dbSNP: rs148271293
Type: single nucleotide variant
Location: chr11:68413729 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.65
Residue 848: the 'beta-propeller 3' region

Full LRP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bone mineral density quantitative trait locus 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: osteoporosis exudative vitreoretinopathy 1 autosomal dominant osteosclerosis, Worth type osteoporosis-pseudoglioma syndrome exudative vitreoretinopathy 4 autosomal dominant osteopetrosis 1 polycystic liver disease 4 with or without kidney cysts

Similar variants

LRP5 p.Pro848Gln Likely pathogenic ★ same residue
LRP5 p.Pro848Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
LRP5 c.1412+1G>A Pathogenic ★★ same condition
LRP5 c.3236+2T>G Pathogenic/Likely pathogenic ★★ same condition
LRP5 c.4488+2T>G Pathogenic/Likely pathogenic ★★ same condition
LRP5 p.Ala214Thr Pathogenic ★★ same condition
LRP5 p.Ala242Thr Pathogenic/Likely pathogenic ★★ same condition
LRP5 p.Ala422Thr 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/lrp5-p-pro848 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown