Is LRP4 p.Cys129= (c.387C>T) pathogenic?

LRP4 p.Cys129= (c.387C>T) is classified Benign/Likely benign in LRP4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-24). Rare (popmax 0.248%, afr); Associated with Cenani-Lenz syndactyly syndrome.

What condition is associated with LRP4 p.Cys129= (c.387C>T)?

LRP4 p.Cys129= (c.387C>T) is associated with Cenani-Lenz syndactyly syndrome, sclerosteosis 2, congenital myasthenic syndrome 17 (ClinVar).

How common is LRP4 p.Cys129= (c.387C>T) in the general population?

LRP4 p.Cys129= (c.387C>T) is rare (popmax 0.248%, afr) (gnomAD).

LRP4 p.Cys129=

c.387C>T · rs80333596 · VCV705290

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.248%, afr)

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 -3.2	GERP -3.7
Overall
CADD	8.157	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.248% African / African-American · 186/75,066 alleles

Filtering AF 0.219% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.207%

Overall 0.0156% 252/1,613,930 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.248%	404
Admixed American	0.0133%	7,503
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Finnishnot grpmax-eligible	0.00784%	12,753
European (non-Finnish)	0.00364%	27,442
South Asian	0.0022%	45,543

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.Cys129=
Coding: c.387C>T
MANE Select: NM_002334
dbSNP: rs80333596
Type: single nucleotide variant
Location: chr11:46899906 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.57 · 1 PDB
Residue 129: a disulfide bond; the ldl-receptor class a 3 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.Cys129Phe 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-cys129 (accessed [today's date]).

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