LBR p.Arg83=
c.249C>T · rs756952587 · VCV2966422
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, mid)
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 -0.21 | GERP -4.9 |
| Overall | ||
| CADD | 7.036 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Middle Eastern · 1/5,986 alleles
Filtering AF
0.0021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.000744%
12/1,613,918 alleles · ultra-rare
exomes 10/1,461,742 · genomes 2/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0167% | 5,986 |
| South Asian | 0.00549% | 18,217 |
| Admixed American | 0.00333% | 30,006 |
| African / African-American | 0.00134% | 74,888 |
| European (non-Finnish) | 0.000254% | 393,345 |
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.Arg83=
- Coding
- c.249C>T
- MANE Select
- NM_002296
- dbSNP
- rs756952587
- Type
- single nucleotide variant
- Location
- chr1:225422194 (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 83
- the 'disordered' region; a UniProt-annotated variant site (in skpha)
Similar variants
- LBR p.Arg83Cys Uncertain significance ★★ ⚠ same residue
- LBR p.Arg83His Uncertain significance ★★ same residue
- LBR p.Arg83Gly Uncertain significance ★ ⚠ same residue
- LBR c.367-2A>C Pathogenic/Likely pathogenic ★★ same type
- LBR p.Arg512Gln Pathogenic/Likely pathogenic ★★ same type
- LBR p.Arg583Gln Pathogenic ★★ same type
- LBR p.Arg586His Pathogenic/Likely pathogenic ★★ same type
- LBR p.Asn547Asp Pathogenic/Likely pathogenic ★★ same type
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-arg83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown