Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 7.83%, afr) — too common for a highly-penetrant pathogenic allele
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 2.3 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 8.784 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.83%
African / African-American · 5,869/74,944 alleles
Filtering AF
7.66%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 7.6%
Overall
0.407%
6,557/1,612,458 alleles · common
exomes 3,267/1,460,146 · genomes 3,290/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 7.83% | 13 |
| Remaining individualsnot grpmax-eligible | 0.509% | 196 |
| Admixed American | 0.464% | 215 |
| Middle Eastern | 0.314% | 319 |
| South Asian | 0.0155% | 6,454 |
| European (non-Finnish) | 0.00509% | 19,660 |
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
- LMBRD2
- Protein
- p.Ser445=
- Coding
- c.1335T>C
- MANE Select
- NM_001007527
- dbSNP
- rs9686339
- Type
- single nucleotide variant
- Location
- chr5:36116561 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.95
Similar variants
- LMBRD2 p.Arg483His Pathogenic/Likely pathogenic ★★ ⚠ same type
- LMBRD2 p.Arg456His Uncertain significance ★★ ⚠ same type
- LMBRD2 p.Arg632Cys Uncertain significance ★★ ⚠ same type
- LMBRD2 p.Gln587Glu Uncertain significance ★★ ⚠ same type
- LMBRD2 p.Glu434Lys Uncertain significance ★★ ⚠ same type
- LMBRD2 p.Ile455Ser Uncertain significance ★★ ⚠ same type
- LMBRD2 p.Leu536Met Uncertain significance ★★ ⚠ same type
- LMBRD2 p.Met224Thr 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/lmbrd2-p-ser445 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown