LEMD3 p.Arg867=
c.2601A>G · rs2498913947 · VCV2829853
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 0.61 | GERP -3.1, phastCons 0.89 |
| Overall | ||
| CADD | 3.841 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,058 alleles
Overall
0.000124%
2/1,612,082 alleles · ultra-rare
exomes 2/1,459,772 · genomes 0/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,058 |
| European (non-Finnish) | 8.49e-05% | 1,178,543 |
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.Arg867=
- Coding
- c.2601A>G
- MANE Select
- NM_014319
- dbSNP
- rs2498913947
- Type
- single nucleotide variant
- Location
- chr12:65246190 (GRCh38)
- Gene constraint
- LOEUF 0.584 · pLI 0.40 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.07 · 3 PDB
- Residue 867
- the 'interaction with smad1, smad2, smad3 and smad5' region; a UniProt-annotated variant site (in bos; patient does not show osteopoikilosis); a UniProt-annotated variant site (in bos)
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-arg867 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown