LEMD3 p.Pro784=
c.2352G>A · VCV3611513
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0067%, eas)
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 -4.5 | GERP -3.5 |
| Overall | ||
| CADD | 5.091 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0067%
East Asian · 3/44,766 alleles
Filtering AF
0.00178%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000893%
Overall
0.00168%
27/1,603,352 alleles · very rare
exomes 26/1,451,208 · genomes 1/152,144 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0067% | 14,922 |
| Remaining individualsnot grpmax-eligible | 0.00644% | 15,533 |
| South Asian | 0.0022% | 45,415 |
| Admixed American | 0.00167% | 59,992 |
| European (non-Finnish) | 0.00137% | 73,152 |
| African / African-American | 0.00134% | 74,690 |
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.Pro784=
- Coding
- c.2352G>A
- MANE Select
- NM_014319
- Type
- single nucleotide variant
- Location
- chr12:65243434 (GRCh38)
- Gene constraint
- LOEUF 0.584 · pLI 0.40 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.07 · 3 PDB
- Residue 784
- the 'interaction with smad1, smad2, smad3 and smad5' region; a UniProt-annotated variant site (in bos; patient does not show osteopoikilosis); a β-strand
Similar variants
- LEMD3 p.Pro784Gln Uncertain significance ★ ⚠ same residue
- LEMD3 p.Arg537Ter Pathogenic ★★ same type
- LEMD3 p.Arg625Ter Pathogenic ★★ same type
- LEMD3 p.Arg655Ter Pathogenic/Likely pathogenic ★★ same type
- LEMD3 p.Arg678Ter Pathogenic/Likely pathogenic ★★ same type
- LEMD3 p.Arg735Ter Pathogenic ★★ same type
- LEMD3 p.Glu601Ter Pathogenic/Likely pathogenic ★★ same type
- LEMD3 p.Tyr441Ter 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/lemd3-p-pro784 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown