Is LRP4 p.Ala47= (c.141C>G) pathogenic?

LRP4 p.Ala47= (c.141C>G) is classified Benign in LRP4 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-24). Rare (popmax 0.641%, sas); Associated with Cenani-Lenz syndactyly syndrome.

What condition is associated with LRP4 p.Ala47= (c.141C>G)?

LRP4 p.Ala47= (c.141C>G) is associated with Cenani-Lenz syndactyly syndrome, sclerosteosis 2, congenital myasthenic syndrome 17 (ClinVar).

How common is LRP4 p.Ala47= (c.141C>G) in the general population?

LRP4 p.Ala47= (c.141C>G) is rare (popmax 0.641%, sas) (gnomAD).

LRP4 p.Ala47=

c.141C>G · rs543418199 · VCV467781

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.641%, sas)

Conditions

Cenani-Lenz syndactyly syndrome

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 0.6	GERP 0.94, phastCons 1
Overall
CADD	8.287	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.641% South Asian · 584/91,082 alleles

Filtering AF 0.598% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.581%

Overall 0.0368% 594/1,614,090 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.641%	156
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	8.47e-05%	1,180,036

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: LRP4
Protein: p.Ala47=
Coding: c.141C>G
MANE Select: NM_002334
dbSNP: rs543418199
Type: single nucleotide variant
Location: chr11:46902841 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.57 · 1 PDB
Residue 47: a disulfide bond; the ldl-receptor class a 1 domain

Full LRP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cenani-Lenz syndactyly syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: sclerosteosis 2 congenital myasthenic syndrome 17

Similar variants

LRP4 p.Ala47Val Uncertain significance ★ ⚠ same residue
LRP4 c.316+1G>A Pathogenic ★★ same condition
LRP4 c.547+1G>A Likely pathogenic ★★ same condition
LRP4 p.Gln944Ter Pathogenic ★★ same condition
LRP4 p.Glu1233Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
LRP4 c.1309+6G>T Uncertain significance ★★ same condition
LRP4 c.2215+5G>A Uncertain significance ★★ same condition
LRP4 c.2216-3C>T Uncertain significance ★★ 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/lrp4-p-ala47 (accessed [today's date]).

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