Is LRP4 p.Ser1003= (c.3009T>C) pathogenic?

LRP4 p.Ser1003= (c.3009T>C) is classified Likely benign in LRP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). Absent from gnomAD v4.1; Associated with Cenani-Lenz syndactyly syndrome.

What condition is associated with LRP4 p.Ser1003= (c.3009T>C)?

LRP4 p.Ser1003= (c.3009T>C) is associated with Cenani-Lenz syndactyly syndrome, sclerosteosis 2, congenital myasthenic syndrome 17 (ClinVar).

How common is LRP4 p.Ser1003= (c.3009T>C) in the general population?

LRP4 p.Ser1003= (c.3009T>C) is absent from gnomAD v4.1 (gnomAD).

LRP4 p.Ser1003=

c.3009T>C · rs2539737097 · VCV2130849

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.4	GERP -2.4, phastCons 0.98
Overall
CADD	9.073	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: LRP4
Protein: p.Ser1003=
Coding: c.3009T>C
MANE Select: NM_002334
dbSNP: rs2539737097
Type: single nucleotide variant
Location: chr11:46879034 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.57 · 1 PDB

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 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
LRP4 c.3277+5G>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-ser1003 (accessed [today's date]).

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