Is LRP2 p.Arg2432= (c.7296A>G) pathogenic?

LRP2 p.Arg2432= (c.7296A>G) is classified Likely benign in LRP2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.066%, mid); Associated with Donnai-Barrow syndrome.

What condition is associated with LRP2 p.Arg2432= (c.7296A>G)?

LRP2 p.Arg2432= (c.7296A>G) is associated with Donnai-Barrow syndrome (ClinVar).

How common is LRP2 p.Arg2432= (c.7296A>G) in the general population?

LRP2 p.Arg2432= (c.7296A>G) is ultra-rare (popmax 0.066%, mid) (gnomAD).

LRP2 p.Arg2432=

c.7296A>G · rs370035430 · VCV708879

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Conditions

Donnai-Barrow syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.94	GERP 1.3, phastCons 1
Overall
CADD	2.944	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0356%

Overall 0.0031% 50/1,614,116 alleles · ultra-rare exomes 30/1,461,794 · genomes 20/152,322 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
African / African-American	0.0533%	1,876
Remaining individualsnot grpmax-eligible	0.008%	12,501
Admixed American	0.00167%	60,026

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: LRP2
Protein: p.Arg2432=
Coding: c.7296A>G
MANE Select: NM_004525
dbSNP: rs370035430
Type: single nucleotide variant
Location: chr2:169206424 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2432: a β-strand

Full LRP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Donnai-Barrow syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LRP2 c.12019+1G>A Likely pathogenic ★★ same condition
LRP2 c.2639+1G>A Pathogenic/Likely pathogenic ★★ same condition
LRP2 c.3667+1G>A Pathogenic/Likely pathogenic ★★ same condition
LRP2 c.8452+1G>A Pathogenic ★★ same condition
LRP2 p.Arg1953Ter Pathogenic/Likely pathogenic ★★ same condition
LRP2 p.Arg2225Ter Pathogenic/Likely pathogenic ★★ same condition
LRP2 p.Arg278Ter Pathogenic/Likely pathogenic ★★ same condition
LRP2 p.Arg3184Ter Pathogenic/Likely pathogenic ★★ 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/lrp2-p-arg2432 (accessed [today's date]).

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