Is LRP5 p.Asp225= (c.675C>T) pathogenic?

LRP5 p.Asp225= (c.675C>T) is classified Benign in LRP5 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-12). Low-frequency (popmax 1.49%, sas); Associated with osteogenesis imperfecta.

What condition is associated with LRP5 p.Asp225= (c.675C>T)?

LRP5 p.Asp225= (c.675C>T) is associated with osteogenesis imperfecta (ClinVar).

How common is LRP5 p.Asp225= (c.675C>T) in the general population?

LRP5 p.Asp225= (c.675C>T) is low-frequency (popmax 1.49%, sas) (gnomAD).

How is Osteogenesis imperfecta inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

LRP5 p.Asp225=

c.675C>T · rs138207107 · VCV742151

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.49%, sas)

Conditions

osteogenesis imperfecta

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 -15	GERP -3.9
Overall
CADD	0.778	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.49% South Asian · 1,353/90,620 alleles

Filtering AF 1.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4%

Overall 0.101% 1,622/1,611,826 alleles · low-frequency exomes 1,490/1,459,476 · genomes 132/152,350 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.49%	67
Middle Eastern	0.153%	655
Remaining individualsnot grpmax-eligible	0.135%	743
African / African-American	0.0707%	1,415
European (non-Finnish)	0.00992%	10,078
Admixed American	0.00501%	19,947
East Asian	0.00447%	22,362
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,534

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.Asp225=
Coding: c.675C>T
MANE Select: NM_002335
dbSNP: rs138207107
Type: single nucleotide variant
Location: chr11:68357836 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.65
Residue 225: the 'beta-propeller 1' region

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

Disease context

osteogenesis imperfecta — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Osteogenesis imperfecta (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

LRP5 c.884-2A>G Likely pathogenic ★★ same condition
LRP5 p.Met1Val Pathogenic/Likely pathogenic ★★ same condition
LRP5 p.Trp1278Ter Pathogenic/Likely pathogenic ★★ same condition
LRP5 p.Ala1265Pro Uncertain significance ★★ ⚠ same condition
LRP5 p.Ala465Thr Uncertain significance ★★ ⚠ same condition
LRP5 p.Arg178Leu Uncertain significance ★★ ⚠ same condition
LRP5 p.Arg398Cys Uncertain significance ★★ ⚠ same condition
LRP5 p.Arg746Gln Uncertain significance ★★ ⚠ 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-asp225 (accessed [today's date]).

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