LARGE1 p.Ala640=
c.1920C>A · rs2145831959 · VCV1572507
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 9.9 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 12.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,040 alleles
Overall
6.19e-05%
1/1,614,242 alleles · very rare
exomes 1/1,461,882 · genomes 0/152,360 · joint denominator
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.Ala640=
- Coding
- c.1920C>A
- MANE Select
- NM_133642
- dbSNP
- rs2145831959
- Type
- single nucleotide variant
- Location
- chr22:33277213 (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 640
- the 'glucuronyltransferase activity' region; an α-helix
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-ala640 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown