Is LBR p.Val317= (c.951A>G) pathogenic?

LBR p.Val317= (c.951A>G) is classified Conflicting classifications of pathogenicity in LBR (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-28). Very rare (popmax 0.00814%, nfe); Associated with Greenberg dysplasia.

What condition is associated with LBR p.Val317= (c.951A>G)?

LBR p.Val317= (c.951A>G) is associated with Greenberg dysplasia (ClinVar).

How common is LBR p.Val317= (c.951A>G) in the general population?

LBR p.Val317= (c.951A>G) is very rare (popmax 0.00814%, nfe) (gnomAD).

How is Greenberg dysplasia inherited?

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

LBR p.Val317=

c.951A>G · rs199748938 · VCV295938

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00814%, nfe)

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 -11	GERP -5.3
Overall
CADD	0.215	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00814% European (non-Finnish) · 96/1,179,854 alleles

Filtering AF 0.00681% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00639% 103/1,612,612 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00814%	12,290
Finnishnot grpmax-eligible	0.00629%	15,904
African / African-American	0.00269%	37,194
Remaining individualsnot grpmax-eligible	0.0016%	62,452

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.Val317=
Coding: c.951A>G
MANE Select: NM_002296
dbSNP: rs199748938
Type: single nucleotide variant
Location: chr1:225412587 (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 317: a UniProt-annotated variant site (in skpha)

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.Val317Ile Likely benign ★★ same residue
LBR p.Val317Ala Uncertain significance ★ ⚠ same residue
LBR p.Val317Leu Uncertain significance ★ ⚠ 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

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-val317 (accessed [today's date]).

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