Is LRP2 p.Pro82Ser (c.244C>T) pathogenic?

LRP2 p.Pro82Ser (c.244C>T) is classified Uncertain significance in LRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely benign (0.1807); Absent from gnomAD v4.1.

How common is LRP2 p.Pro82Ser (c.244C>T) in the general population?

LRP2 p.Pro82Ser (c.244C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LRP2 p.Pro82Ser (c.244C>T)?

AlphaMissense predicts likely benign (score 0.1807) — an in-silico prediction, not a clinical call.

LRP2 p.Pro82Ser

c.244C>T · rs2528664586 · VCV2127634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1807 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.1807	likely benign
REVEL	0.636	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.7	GERP -0.62, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 156 kb · p 7.9e-06 · regional, not allelic
Overall
CADD	15.3	PHRED · no single calibrated threshold — expert panels disagree

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.Pro82Ser
Coding: c.244C>T
MANE Select: NM_004525
dbSNP: rs2528664586
Type: single nucleotide variant
Location: chr2:169318828 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 82: the ldl-receptor class a 2 domain

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

Similar variants

LRP2 p.Pro82Thr Uncertain significance ★★ same residue
LRP2 p.Pro82= Likely benign ★★ same residue
LRP2 c.12019+1G>A Likely pathogenic ★★ same type
LRP2 c.2639+1G>A Pathogenic/Likely pathogenic ★★ same type
LRP2 c.3667+1G>A Pathogenic/Likely pathogenic ★★ same type
LRP2 c.8452+1G>A Pathogenic ★★ same type
LRP2 p.Arg1953Ter Pathogenic/Likely pathogenic ★★ same type
LRP2 p.Arg2095Ter Pathogenic/Likely pathogenic ★★ 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-pro82ser (accessed [today's date]).

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