Is LRP2 p.Arg938Pro (c.2813G>C) pathogenic?

LRP2 p.Arg938Pro (c.2813G>C) is classified Uncertain significance in LRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-07). AlphaMissense: likely pathogenic (0.8732); Absent from gnomAD v4.1; Associated with Donnai-Barrow syndrome.

What condition is associated with LRP2 p.Arg938Pro (c.2813G>C)?

LRP2 p.Arg938Pro (c.2813G>C) is associated with Donnai-Barrow syndrome (ClinVar).

How common is LRP2 p.Arg938Pro (c.2813G>C) in the general population?

LRP2 p.Arg938Pro (c.2813G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LRP2 p.Arg938Pro (c.2813G>C)?

AlphaMissense predicts likely pathogenic (score 0.8732) — an in-silico prediction, not a clinical call.

LRP2 p.Arg938Pro

c.2813G>C · VCV3584877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8732 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Donnai-Barrow syndrome

Computational evidence

Protein change
AlphaMissense	0.8732	likely pathogenic
REVEL	0.797	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -3.8, phastCons 0.99
Regional constraint	o/e 0.92	unconstrained · MANE · 156 kb · p 7.9e-06 · regional, not allelic
Overall
CADD	18.81	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: LRP2
Protein: p.Arg938Pro
Coding: c.2813G>C
MANE Select: NM_004525
Type: single nucleotide variant
Location: chr2:169247473 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 938: 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 p.Arg938Gln Conflicting classifications of pathogenicity ★ same residue
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

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-arg938pro (accessed [today's date]).

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