LBR p.Ala414=
c.1242T>C · rs1011396281 · VCV2182209
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0267%, afr)
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 -3.7 | GERP -5.3 |
| Overall | ||
| CADD | 0.099 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0267%
African / African-American · 20/74,936 alleles
Filtering AF
0.0177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0147%
Overall
0.0013%
21/1,614,106 alleles · ultra-rare
exomes 12/1,461,872 · genomes 9/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0267% | 3,747 |
| Admixed American | 0.00167% | 60,008 |
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.Ala414=
- Coding
- c.1242T>C
- MANE Select
- NM_002296
- dbSNP
- rs1011396281
- Type
- single nucleotide variant
- Location
- chr1:225410363 (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 414
- a UniProt-annotated variant site (in skpha)
Similar variants
- LBR p.Ala414Thr 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
- LBR p.Asn547Ser Pathogenic/Likely pathogenic ★★ same type
- LBR c.*1586G>A Uncertain significance ★★ 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-ala414 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown