LARGE1 p.Thr55=
c.165G>C · rs63446460 · VCV158805
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.68%, afr)
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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -4.2 |
| Overall | ||
| CADD | 0.219 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.68%
African / African-American · 3,509/75,036 alleles
Filtering AF
4.55%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.49%
Overall
0.261%
4,184/1,604,364 alleles · low-frequency
exomes 2,120/1,452,062 · genomes 2,064/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.68% | 21 |
| Remaining individualsnot grpmax-eligible | 0.42% | 238 |
| Admixed American | 0.42% | 238 |
| Middle Eastern | 0.386% | 259 |
| South Asian | 0.0264% | 3,794 |
| European (non-Finnish) | 0.00941% | 10,630 |
| Finnishnot grpmax-eligible | 0.00547% | 18,277 |
| East Asian | 0.00223% | 44,866 |
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.Thr55=
- Coding
- c.165G>C
- MANE Select
- NM_133642
- dbSNP
- rs63446460
- Type
- single nucleotide variant
- Location
- chr22:33650610 (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 55
- the 'disordered' region
Similar variants
- LARGE1 p.Thr55Lys Uncertain significance ★★ ⚠ same residue
- LARGE1 p.Thr55Ala Benign/Likely benign ★★ same residue
- LARGE1 p.Thr55Met Uncertain significance ★ ⚠ same residue
- LARGE1 p.Thr55Arg 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
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-thr55 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown