Is LRP4 p.Ser100= (c.300G>A) pathogenic?

LRP4 p.Ser100= (c.300G>A) is classified Benign in LRP4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-19). Low-frequency (popmax 1.7%, afr); Associated with Cenani-Lenz syndactyly syndrome.

What condition is associated with LRP4 p.Ser100= (c.300G>A)?

LRP4 p.Ser100= (c.300G>A) is associated with Cenani-Lenz syndactyly syndrome, sclerosteosis 2, congenital myasthenic syndrome 17 (ClinVar).

How common is LRP4 p.Ser100= (c.300G>A) in the general population?

LRP4 p.Ser100= (c.300G>A) is low-frequency (popmax 1.7%, afr) (gnomAD).

LRP4 p.Ser100=

c.300G>A · rs61745166 · VCV304902

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.7%, 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 -20	GERP -3.7
Overall
CADD	0.221	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.7% African / African-American · 1,277/75,024 alleles

Filtering AF 1.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.59%

Overall 0.102% 1,640/1,613,816 alleles · low-frequency exomes 895/1,461,524 · genomes 745/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.7%	59
Amishnot grpmax-eligible	1.64%	61
Admixed American	0.152%	660
Remaining individualsnot grpmax-eligible	0.147%	679
Middle Eastern	0.132%	757
European (non-Finnish)	0.0129%	7,761
South Asian	0.00549%	18,216

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.Ser100=
Coding: c.300G>A
MANE Select: NM_002334
dbSNP: rs61745166
Type: single nucleotide variant
Location: chr11:46900278 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.57 · 1 PDB
Residue 100: the ldl-receptor class a 2 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.Ser100Leu 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-ser100 (accessed [today's date]).

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