Is LRP5 p.Phe70Ter (c.209_210delinsAA) pathogenic?

LRP5 p.Phe70Ter (c.209210delinsAA) is classified Pathogenic/Likely pathogenic in LRP5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-10). Absent from gnomAD; Associated with LRP5-related disorder.

What condition is associated with LRP5 p.Phe70Ter (c.209_210delinsAA)?

LRP5 p.Phe70Ter (c.209_210delinsAA) is associated with LRP5-related disorder, autosomal dominant osteosclerosis, Worth type, osteoporosis-pseudoglioma syndrome (ClinVar).

How common is LRP5 p.Phe70Ter (c.209_210delinsAA) in the general population?

LRP5 p.Phe70Ter (c.209_210delinsAA) is absent from gnomAD (gnomAD).

LRP5 p.Phe70Ter

c.209_210delinsAA · rs2098614719 · VCV865885

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

LRP5-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 4.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LRP5
Protein: p.Phe70Ter
Coding: c.209_210delinsAA
MANE Select: NM_002335
dbSNP: rs2098614719
Type: Indel
Location: chr11:68347964 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.65
Residue 70: the 'beta-propeller 1' region

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

Disease context

LRP5-related disorder

Also linked: 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.Phe70Leu Pathogenic ★ ⚠ same residue
LRP5 p.Phe70Tyr Pathogenic ★ same residue
LRP5 p.Gly404Ala Uncertain significance ★ same condition
LRP5 p.Phe70= Likely benign ★ same residue
LRP5 c.3236+2T>G Pathogenic/Likely pathogenic ★★ same condition
LRP5 c.4488+2_4488+17del Pathogenic/Likely pathogenic ★★ same condition
LRP5 c.4488+2T>G Pathogenic/Likely pathogenic ★★ same condition
LRP5 p.Ala214Thr 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-phe70ter (accessed [today's date]).

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