LARGE1 p.Leu161=
c.483G>A · rs987732719 · VCV1597209
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
1
muscular dystrophy-dystroglycanopathy type B6
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 0.46 | GERP -0.051, phastCons 0.99 |
| Overall | ||
| CADD | 9.676 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,022 alleles
Overall
0.000124%
2/1,613,952 alleles · very rare
exomes 2/1,461,638 · genomes 0/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,022 |
| European (non-Finnish) | 8.48e-05% | 1,179,820 |
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
- LARGE1
- Protein
- p.Leu161=
- Coding
- c.483G>A
- MANE Select
- NM_133642
- dbSNP
- rs987732719
- Type
- single nucleotide variant
- Location
- chr22:33626252 (GRCh38)
- Gene constraint
- LOEUF 0.606 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.15 · 4 PDB
- Residue 161
- an α-helix; the 'xylosyltransferase activity' region
Similar variants
- LARGE1 p.Arg95Ter Pathogenic ★★ same condition
- LARGE1 p.Glu509Lys Pathogenic/Likely pathogenic ★★ same condition
- LARGE1 c.*155C>T Uncertain significance ★★ same condition
- LARGE1 p.Ala149Ser Uncertain significance ★★ ⚠ same condition
- LARGE1 p.Ala252Val Uncertain significance ★★ ⚠ same condition
- LARGE1 p.Ala478Thr Uncertain significance ★★ ⚠ same condition
- LARGE1 p.Ala635Thr Uncertain significance ★★ ⚠ same condition
- LARGE1 p.Ala752Gly 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/large1-p-leu161 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown