Is LBR p.Pro87= (c.261T>C) pathogenic?

LBR p.Pro87= (c.261T>C) is classified Benign in LBR (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 90.6%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Reynolds syndrome.

What condition is associated with LBR p.Pro87= (c.261T>C)?

LBR p.Pro87= (c.261T>C) is associated with Reynolds syndrome, Pelger-Huet anomaly, Greenberg dysplasia (ClinVar).

How is Reynolds syndrome inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

LBR p.Pro87=

Q: How common is LBR p.Pro87= (c.261T>C) in the general population?

LBR p.Pro87= (c.261T>C) is common (popmax 90.6%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.261T>C · rs1056608 · VCV258617

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 90.6%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Reynolds syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.9	GERP -5.3
Overall
CADD	1.232	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 90.6% East Asian · 40,665/44,880 alleles

Filtering AF 89.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 89.6%

Overall 76.7% 1,237,784/1,613,514 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	90.6%	1
Ashkenazi Jewishnot grpmax-eligible	85.9%	1
Admixed American	83.7%	1
Middle Eastern	82.6%	1
European (non-Finnish)	78.8%	1
Finnishnot grpmax-eligible	77.5%	1
Remaining individualsnot grpmax-eligible	77.3%	1
Amishnot grpmax-eligible	72%	1
South Asian	65.2%	2
African / African-American	38.6%	3

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: LBR
Protein: p.Pro87=
Coding: c.261T>C
MANE Select: NM_002296
dbSNP: rs1056608
Type: single nucleotide variant
Location: chr1:225422182 (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 87: the 'disordered' region; a UniProt-annotated variant site (in skpha)

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

Disease context

Reynolds syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Pelger-Huet anomaly Greenberg dysplasia

For Reynolds syndrome (Orphanet):

Inheritance: Not applicable
Onset: Adult

Similar variants

LBR p.Arg512Gln Pathogenic/Likely pathogenic ★★ same condition
LBR p.Arg583Gln Pathogenic ★★ same condition
LBR p.Arg586His Pathogenic/Likely pathogenic ★★ same condition
LBR p.Asn547Asp Pathogenic/Likely pathogenic ★★ same condition
LBR p.Asn547Ser Pathogenic/Likely pathogenic ★★ same condition
LBR c.*1586G>A Uncertain significance ★★ same condition
LBR p.Ala521Ser Uncertain significance ★★ ⚠ same condition
LBR p.Ala521Thr 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/lbr-p-pro87 (accessed [today's date]).

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