Is LRP5 p.Pro5Ala (c.13C>G) pathogenic?

LRP5 p.Pro5Ala (c.13C>G) is classified Uncertain significance in LRP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely benign (0.0503); No allele count reported in gnomAD v4.1 (AN 1,050,088).

How common is LRP5 p.Pro5Ala (c.13C>G) in the general population?

LRP5 p.Pro5Ala (c.13C>G) is no allele count reported in gnomAD v4.1 (AN 1,050,088) (gnomAD).

What do computational predictors say about LRP5 p.Pro5Ala (c.13C>G)?

AlphaMissense predicts likely benign (score 0.0503) — an in-silico prediction, not a clinical call.

LRP5 p.Pro5Ala

c.13C>G · rs2496190917 · VCV1999684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0503 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,050,088)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0503	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 0.29, phastCons 1
Regional constraint	o/e 1.87	unconstrained · MANE · 79 bp · p 1e-05 · regional, not allelic
Overall
CADD	18.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,050,088). 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.Pro5Ala
Coding: c.13C>G
MANE Select: NM_002335
dbSNP: rs2496190917
Type: single nucleotide variant
Location: chr11:68312727 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.65

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

Similar variants

LRP5 p.Pro5= Likely benign ★★ same residue
LRP5 p.Pro5Leu 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
LRP5 p.Ala214Thr 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-pro5ala (accessed [today's date]).

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