Is LPP p.Cys468Arg (c.1402T>C) pathogenic?

LPP p.Cys468Arg (c.1402T>C) is classified Uncertain significance in LPP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1.

How common is LPP p.Cys468Arg (c.1402T>C) in the general population?

LPP p.Cys468Arg (c.1402T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LPP p.Cys468Arg (c.1402T>C)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

LPP p.Cys468Arg

c.1402T>C · VCV3867873

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic · top 4% in LPP
REVEL	0.771	pathogenic-leaning
SaProt	LLR -15.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 468 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	31.0	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 and SaProt are independent agreement signals.

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: LPP
Protein: p.Cys468Arg
Coding: c.1402T>C
MANE Select: NM_001375462
Type: single nucleotide variant
Location: chr3:188760274 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99
Residue 468: the lim zinc-binding 1 domain

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

Similar variants

LPP p.Arg140Trp Uncertain significance ★★ ⚠ same type
LPP c.1113+51T>C Benign ★★ same type
LPP c.1240+249G>A Benign ★★ same type
LPP c.1240+75A>G Benign ★★ same type
LPP c.1410+155C>T Benign ★★ same type
LPP c.1410+157T>C Benign ★★ same type
LPP c.1410+162G>A Benign ★★ same type
LPP c.1410+165T>C 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/lpp-p-cys468arg (accessed [today's date]).

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