LEMD3 p.Pro794=
c.2382C>T · rs905818225 · VCV2170993
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP -0.63, phastCons 0.99 |
| Overall | ||
| CADD | 11.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
South Asian · 3/90,034 alleles
Filtering AF
0.000885%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000445%
Overall
0.000702%
11/1,566,906 alleles · very rare
exomes 10/1,414,848 · genomes 1/152,058 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00333% | 30,011 |
| Remaining individualsnot grpmax-eligible | 0.00329% | 30,438 |
| Admixed American | 0.00167% | 59,938 |
| European (non-Finnish) | 0.00044% | 227,489 |
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.Pro794=
- Coding
- c.2382C>T
- MANE Select
- NM_014319
- dbSNP
- rs905818225
- Type
- single nucleotide variant
- Location
- chr12:65243464 (GRCh38)
- Gene constraint
- LOEUF 0.584 · pLI 0.40 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.07 · 3 PDB
- Residue 794
- the 'interaction with smad1, smad2, smad3 and smad5' region; a UniProt-annotated variant site (in bos; patient does not show osteopoikilosis); an α-helix
Similar variants
- 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
- LEMD3 p.Ala127Val 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/lemd3-p-pro794 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown