Is LRP2 p.Pro2896fs (c.8687del) pathogenic?

LRP2 p.Pro2896fs (c.8687del) is classified Likely pathogenic in LRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-03-14). No gnomAD frequency available for this variant.

How common is LRP2 p.Pro2896fs (c.8687del) in the general population?

LRP2 p.Pro2896fs (c.8687del) is no gnomAD frequency available for this variant (gnomAD).

LRP2 p.Pro2896fs

c.8687del · rs1574121486 · VCV818071

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 46 of 79
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -1.7, phastCons 0.029

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LRP2
Protein: p.Pro2896fs
Coding: c.8687del
MANE Select: NM_004525
dbSNP: rs1574121486
Type: Deletion
Location: chr2:169196922 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2896: the ldl-receptor class a 20 domain

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

Similar variants

LRP2 p.Pro2896Thr Uncertain significance ★ same residue
LRP2 c.427+1del Likely pathogenic ★★ same type
LRP2 p.Pro4380fs Pathogenic/Likely pathogenic ★★ same type
LRP2 c.11498-13del Benign ★★ same type
LRP2 c.13729-12del Benign/Likely benign ★★ same type
LRP2 c.428-10_428-8del Benign/Likely benign ★★ same type
LRP2 c.428-11_428-8del Benign/Likely benign ★★ same type
LRP2 c.428-12_428-8del Likely benign ★★ same type

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-pro2896fs (accessed [today's date]).

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