Is LBR p.Val39= (c.117G>A) pathogenic?

LBR p.Val39= (c.117G>A) is classified Benign in LBR (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 78.2%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Reynolds syndrome.

What condition is associated with LBR p.Val39= (c.117G>A)?

LBR p.Val39= (c.117G>A) 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.Val39=

Q: How common is LBR p.Val39= (c.117G>A) in the general population?

LBR p.Val39= (c.117G>A) is common (popmax 78.2%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.117G>A · rs1056607 · VCV258616

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 78.2%, amr) — 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 -4.1	GERP -4.7
Overall
CADD	0.431	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 78.2% Admixed American · 46,920/60,012 alleles

Filtering AF 77.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 77.3%

Overall 71.9% 1,159,565/1,612,512 alleles · common exomes 1,051,372/1,460,430 · genomes 108,193/152,082 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	78.6%	1
Admixed Americangrpmax	78.2%	1
East Asian	77.1%	1
Middle Eastern	74.9%	1
Ashkenazi Jewishnot grpmax-eligible	74.6%	1
European (non-Finnish)	73%	1
Remaining individualsnot grpmax-eligible	72.1%	1
Amishnot grpmax-eligible	71.8%	1
African / African-American	63.9%	2
South Asian	52.1%	2

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val39=
Coding: c.117G>A
MANE Select: NM_002296
dbSNP: rs1056607
Type: single nucleotide variant
Location: chr1:225423959 (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 39: the tudor domain; a β-strand

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-val39 (accessed [today's date]).

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