Is LRP5 p.Pro628= (c.1884C>T) pathogenic?

LRP5 p.Pro628= (c.1884C>T) is classified Likely benign in LRP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). Absent from gnomAD v4.1.

How common is LRP5 p.Pro628= (c.1884C>T) in the general population?

LRP5 p.Pro628= (c.1884C>T) is absent from gnomAD v4.1 (gnomAD).

LRP5 p.Pro628=

c.1884C>T · rs2153164629 · VCV1157730

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 1.7	GERP 0.69, phastCons 1
Overall
CADD	12.26	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.Pro628=
Coding: c.1884C>T
MANE Select: NM_002335
dbSNP: rs2153164629
Type: single nucleotide variant
Location: chr11:68406606 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.65
Residue 628: the egf-like 2 domain

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

Similar variants

LRP5 p.Pro628Ala Uncertain significance ★ ⚠ same residue
LRP5 p.Pro628Leu Uncertain significance ★ ⚠ same residue
LRP5 p.Pro628Ser Uncertain significance ★ ⚠ same residue
LRP5 c.1412+1G>A Pathogenic ★★ same type
LRP5 c.2827+1G>A Pathogenic ★★ same type
LRP5 c.3236+2T>G Pathogenic/Likely pathogenic ★★ same type
LRP5 c.4488+2T>G Pathogenic/Likely pathogenic ★★ same type
LRP5 c.884-2A>G Likely pathogenic ★★ same type

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-pro628 (accessed [today's date]).

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