Is LRP5 p.Pro1284= (c.3852C>T) pathogenic?

LRP5 p.Pro1284= (c.3852C>T) is classified Likely benign in LRP5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-28). Ultra-rare (popmax 0.0165%, mid); Associated with exudative vitreoretinopathy 1.

What condition is associated with LRP5 p.Pro1284= (c.3852C>T)?

LRP5 p.Pro1284= (c.3852C>T) is associated with exudative vitreoretinopathy 1, osteoporosis, autosomal dominant osteosclerosis, Worth type (ClinVar).

How common is LRP5 p.Pro1284= (c.3852C>T) in the general population?

LRP5 p.Pro1284= (c.3852C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

LRP5 p.Pro1284=

c.3852C>T · rs144115017 · VCV1103151

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

exudative vitreoretinopathy 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 -9.2	GERP -5.3
Overall
CADD	2.274	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00248% 40/1,613,292 alleles · ultra-rare exomes 32/1,460,932 · genomes 8/152,360 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.00439%	22,773
African / African-American	0.004%	25,018
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Remaining individualsnot grpmax-eligible	0.0032%	31,249
European (non-Finnish)	0.00237%	42,142
East Asian	0.00223%	44,882

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.Pro1284=
Coding: c.3852C>T
MANE Select: NM_002335
dbSNP: rs144115017
Type: single nucleotide variant
Location: chr11:68433690 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.65
Residue 1284: the ldl-receptor class a 1 domain

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

Disease context

exudative vitreoretinopathy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: osteoporosis 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.Pro1284Ser Uncertain significance ★ ⚠ 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
LRP5 p.Arg1078Ter 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-pro1284 (accessed [today's date]).

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