LARGE1 p.Glu236=
c.708G>A · rs202028671 · VCV717804
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, afr)
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 1.9 | GERP -3.4, phastCons 1 |
| Overall | ||
| CADD | 9.351 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
African / African-American · 37/75,048 alleles
Filtering AF
0.0368%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0324%
Overall
0.00285%
46/1,614,124 alleles · ultra-rare
exomes 30/1,461,804 · genomes 16/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0493% | 2,028 |
| Middle Eastern | 0.033% | 3,031 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,625 |
| South Asian | 0.0022% | 45,544 |
| European (non-Finnish) | 8.47e-05% | 1,179,956 |
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.Glu236=
- Coding
- c.708G>A
- MANE Select
- NM_133642
- dbSNP
- rs202028671
- Type
- single nucleotide variant
- Location
- chr22:33564927 (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 236
- 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-glu236 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown