Is LBR p.Pro569Arg (c.1706C>G) pathogenic?

LBR p.Pro569Arg (c.1706C>G) is classified Pathogenic in LBR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2003-11-01). AlphaMissense: likely pathogenic (0.9426); Absent from gnomAD v4.1; Associated with Pelger-Huet anomaly.

What condition is associated with LBR p.Pro569Arg (c.1706C>G)?

LBR p.Pro569Arg (c.1706C>G) is associated with Pelger-Huet anomaly (ClinVar).

How common is LBR p.Pro569Arg (c.1706C>G) in the general population?

LBR p.Pro569Arg (c.1706C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LBR p.Pro569Arg (c.1706C>G)?

AlphaMissense predicts likely pathogenic (score 0.9426) — an in-silico prediction, not a clinical call.

LBR p.Pro569Arg

c.1706C>G · rs137852606 · VCV9532

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9426 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Pelger-Huet anomaly

Computational evidence

Protein change
AlphaMissense	0.9426	likely pathogenic ✓ concordant with ClinVar · top 6% in LBR
REVEL	0.949	strongly pathogenic-leaning
SaProt	LLR -16.97	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 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 21 kb · p 0.12 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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: LBR
Protein: p.Pro569Arg
Coding: c.1706C>G
MANE Select: NM_002296
dbSNP: rs137852606
Type: single nucleotide variant
Location: chr1:225403445 (GRCh38)
Gene constraint: LOEUF 0.499 · pLI 0.97 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.89 · 1 PDB
Residue 569: a UniProt-annotated variant site (in skpha); a UniProt-annotated variant site (in pha)

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

Disease context

Pelger-Huet anomaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LBR p.Pro569Ser Uncertain significance ★ ⚠ same residue
LBR p.Arg586His Pathogenic/Likely pathogenic ★★ same condition
LBR p.Asn547Asp Pathogenic/Likely pathogenic ★★ same condition
LBR p.Arg169Cys Uncertain significance ★★ ⚠ same condition
LBR p.Ile287Thr Uncertain significance ★★ ⚠ same condition
LBR p.Tyr366Cys Uncertain significance ★★ ⚠ same condition
LBR c.1315-13T>C Likely benign ★★ same condition
LBR p.Pro87= Benign ★★ 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/lbr-p-pro569arg (accessed [today's date]).

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