Is LRP2 p.Arg233Ter (c.697C>T) pathogenic?

LRP2 p.Arg233Ter (c.697C>T) is classified Pathogenic in LRP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-12). Very rare (popmax 8.48e-05%, nfe); Associated with Fetal anomalies with a likely genetic cause.

What condition is associated with LRP2 p.Arg233Ter (c.697C>T)?

LRP2 p.Arg233Ter (c.697C>T) is associated with Fetal anomalies with a likely genetic cause (ClinVar).

How common is LRP2 p.Arg233Ter (c.697C>T) in the general population?

LRP2 p.Arg233Ter (c.697C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

LRP2 p.Arg233Ter

c.697C>T · rs1230676326 · VCV2740386

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Fetal anomalies with a likely genetic cause

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 7 of 79
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.69	GERP -3.4, phastCons 0.075
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,932 alleles

Overall 6.2e-05% 1/1,613,900 alleles · very rare exomes 1/1,461,782 · genomes 0/152,118 · joint denominator

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.Arg233Ter
Coding: c.697C>T
MANE Select: NM_004525
dbSNP: rs1230676326
Type: single nucleotide variant
Location: chr2:169292325 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 233: the ldl-receptor class a 6 domain

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

Disease context

Fetal anomalies with a likely genetic cause

Similar variants

LRP2 p.Arg233Gln Uncertain significance ★★ same residue
LRP2 p.Arg2095Ter Pathogenic/Likely pathogenic ★★ same condition
LRP2 p.Arg3554Ter Pathogenic/Likely pathogenic ★★ same condition
LRP2 p.Arg2013His Uncertain significance ★★ ⚠ same condition
LRP2 p.Asp3951Asn Uncertain significance ★★ same condition
LRP2 p.Gly304Arg Uncertain significance ★★ same condition
LRP2 p.Ile1683Thr Uncertain significance ★★ same condition
LRP2 p.Lys3363Gln 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/lrp2-p-arg233ter (accessed [today's date]).

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