Is LRP5 p.Val387= (c.1161C>T) pathogenic?

LRP5 p.Val387= (c.1161C>T) is classified Conflicting classifications of pathogenicity in LRP5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-02). Absent from gnomAD v4.1; Associated with autosomal dominant osteopetrosis 1.

What condition is associated with LRP5 p.Val387= (c.1161C>T)?

LRP5 p.Val387= (c.1161C>T) is associated with autosomal dominant osteopetrosis 1, autosomal dominant osteosclerosis, Worth type, osteoporosis-pseudoglioma syndrome (ClinVar).

How common is LRP5 p.Val387= (c.1161C>T) in the general population?

LRP5 p.Val387= (c.1161C>T) is absent from gnomAD v4.1 (gnomAD).

LRP5 p.Val387=

c.1161C>T · rs2496598396 · VCV2030121

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal dominant osteopetrosis 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 -0.7	GERP -3.9, phastCons 0.005
Overall
CADD	1.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LRP5
Protein: p.Val387=
Coding: c.1161C>T
MANE Select: NM_002335
dbSNP: rs2496598396
Type: single nucleotide variant
Location: chr11:68386461 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.65
Residue 387: the 'beta-propeller 2' region

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

Disease context

autosomal dominant osteopetrosis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

LRP5 p.Val387Ala Uncertain significance ★ ⚠ same residue
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
LRP5 p.Arg353Gln Pathogenic/Likely pathogenic ★★ same condition
LRP5 p.Arg428Ter 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-val387 (accessed [today's date]).

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