Is LARGE1 p.Arg53fs (c.156dup) pathogenic?

LARGE1 p.Arg53fs (c.156dup) is classified Pathogenic in LARGE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-17). No gnomAD frequency available for this variant; Associated with muscular dystrophy-dystroglycanopathy type B6.

What condition is associated with LARGE1 p.Arg53fs (c.156dup)?

LARGE1 p.Arg53fs (c.156dup) is associated with muscular dystrophy-dystroglycanopathy type B6 (ClinVar).

How common is LARGE1 p.Arg53fs (c.156dup) in the general population?

LARGE1 p.Arg53fs (c.156dup) is no gnomAD frequency available for this variant (gnomAD).

LARGE1 p.Arg53fs

c.156dup · rs2080771312 · VCV2806164

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

muscular dystrophy-dystroglycanopathy type B6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -4.2, phastCons 0.79

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LARGE1
Protein: p.Arg53fs
Coding: c.156dup
MANE Select: NM_133642
dbSNP: rs2080771312
Type: Duplication
Location: chr22:33650618 (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 53: the 'disordered' region

Full LARGE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

muscular dystrophy-dystroglycanopathy type B6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LARGE1 p.Arg53= Likely benign ★ same residue
LARGE1 p.Leu85_Ala86dup Uncertain significance ★★ same condition
LARGE1 p.Ala256fs Pathogenic ★ same condition
LARGE1 p.Glu61fs Pathogenic ★ same condition
LARGE1 p.Leu514fs Pathogenic ★ same condition
LARGE1 p.Trp316fs Pathogenic ★ same condition
LARGE1 c.1287+2dup Uncertain significance ★ same condition
LARGE1 c.1452-13dup Likely benign ★ 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-arg53fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown