LARGE1 p.Ile533=
c.1599C>T · rs12627793 · VCV211369
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.294%, eas)
Conditions
2
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 -0.085 | GERP -3.7, phastCons 0.15 |
| Overall | ||
| CADD | 8.687 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.294%
East Asian · 132/44,888 alleles
Filtering AF
0.253%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.238%
Overall
0.024%
387/1,614,264 alleles · rare
exomes 359/1,461,894 · genomes 28/152,370 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.294% | 340 |
| South Asian | 0.201% | 498 |
| Middle Eastern | 0.066% | 1,516 |
| Remaining individualsnot grpmax-eligible | 0.0272% | 3,677 |
| Admixed American | 0.005% | 20,009 |
| African / African-American | 0.004% | 25,025 |
| European (non-Finnish) | 0.00364% | 27,443 |
| Finnishnot grpmax-eligible | 0.00312% | 32,023 |
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.Ile533=
- Coding
- c.1599C>T
- MANE Select
- NM_133642
- dbSNP
- rs12627793
- Type
- single nucleotide variant
- Location
- chr22:33304360 (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 533
- the 'glucuronyltransferase activity' region; a β-strand
Similar variants
- LARGE1 p.Ile533Val Uncertain significance ★★ ⚠ same residue
- 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
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-ile533 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown