LEMD3 p.Val182=
c.546G>A · rs576557496 · VCV1162147
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0138%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.50 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.33 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 3.7 | GERP 0.83, phastCons 1 |
| Overall | ||
| CADD | 18.29 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0138%
Admixed American · 5/36,250 alleles
Filtering AF
0.00539%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00352%
Overall
0.000475%
7/1,474,192 alleles · ultra-rare
exomes 3/1,322,002 · genomes 4/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0138% | 7,250 |
| Remaining individualsnot grpmax-eligible | 0.00352% | 28,446 |
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.Val182=
- Coding
- c.546G>A
- MANE Select
- NM_014319
- dbSNP
- rs576557496
- Type
- single nucleotide variant
- Location
- chr12:65170142 (GRCh38)
- Gene constraint
- LOEUF 0.584 · pLI 0.40 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.07 · 3 PDB
- Residue 182
- the 'disordered' region
Similar variants
- LEMD3 p.Val182Leu 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-val182 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown