Is LBR p.Pro119= (c.357G>A) pathogenic?

LBR p.Pro119= (c.357G>A) is classified Conflicting classifications of pathogenicity in LBR (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2022-10-24). Ultra-rare (popmax 0.0955%, sas); Associated with Greenberg dysplasia.

What condition is associated with LBR p.Pro119= (c.357G>A)?

LBR p.Pro119= (c.357G>A) is associated with Greenberg dysplasia (ClinVar).

How common is LBR p.Pro119= (c.357G>A) in the general population?

LBR p.Pro119= (c.357G>A) is ultra-rare (popmax 0.0955%, sas) (gnomAD).

How is Greenberg dysplasia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

LBR p.Pro119=

c.357G>A · rs150177807 · VCV877056

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0955%, sas)

Conditions

Greenberg dysplasia

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 -7.4	GERP -5.3
Overall
CADD	3.881	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0955% South Asian · 87/91,078 alleles

Filtering AF 0.0793% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0733%

Overall 0.00806% 130/1,613,882 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0955%	1,047
Middle Eastern	0.0166%	6,036
African / African-American	0.016%	6,252
Admixed American	0.00833%	12,004
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.00186%	53,633
Finnishnot grpmax-eligible	0.00157%	63,888

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.Pro119=
Coding: c.357G>A
MANE Select: NM_002296
dbSNP: rs150177807
Type: single nucleotide variant
Location: chr1:225422086 (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 119: 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

Greenberg dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Greenberg dysplasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal

Similar variants

LBR p.Pro119Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro119 (accessed [today's date]).

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