LEMD3 p.Pro115=
c.345A>G · rs530591432 · VCV310220
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0419%, mid)
Conditions
1
Buschke-Ollendorff 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 -0.54 | GERP -3 |
| Overall | ||
| CADD | 3.978 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0419%
Middle Eastern · 2/4,774 alleles
Filtering AF
0.0146%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0119%
Overall
0.00956%
139/1,453,454 alleles · ultra-rare
exomes 122/1,301,422 · genomes 17/152,032 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0419% | 2,387 |
| South Asian | 0.0233% | 4,288 |
| Remaining individualsnot grpmax-eligible | 0.0161% | 6,197 |
| European (non-Finnish) | 0.00981% | 10,193 |
| Admixed American | 0.00596% | 16,790 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0045% | 22,200 |
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
- LEMD3
- Protein
- p.Pro115=
- Coding
- c.345A>G
- MANE Select
- NM_014319
- dbSNP
- rs530591432
- Type
- single nucleotide variant
- Location
- chr12:65169941 (GRCh38)
- Gene constraint
- LOEUF 0.584 · pLI 0.40 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.07 · 3 PDB
- Residue 115
- the 'disordered' region
Similar variants
- LEMD3 p.Arg678Ter Pathogenic/Likely pathogenic ★★ same condition
- LEMD3 p.Glu601Ter Pathogenic/Likely pathogenic ★★ same condition
- LEMD3 p.Ala127Val Uncertain significance ★★ ⚠ same condition
- LEMD3 p.Asn257Asp Uncertain significance ★★ ⚠ same condition
- LEMD3 p.Asn529Ser Uncertain significance ★★ ⚠ same condition
- LEMD3 p.Asp214Tyr Uncertain significance ★★ ⚠ same condition
- LEMD3 p.Asp544Ala Uncertain significance ★★ ⚠ same condition
- LEMD3 p.Asp755Asn 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/lemd3-p-pro115 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown