Is LARGE1 p.Ser33fs (c.96del) pathogenic?

LARGE1 p.Ser33fs (c.96del) is classified Pathogenic in LARGE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-28). No gnomAD frequency available for this variant; Associated with muscular dystrophy-dystroglycanopathy type B6.

What condition is associated with LARGE1 p.Ser33fs (c.96del)?

LARGE1 p.Ser33fs (c.96del) is associated with muscular dystrophy-dystroglycanopathy type B6 (ClinVar).

How common is LARGE1 p.Ser33fs (c.96del) in the general population?

LARGE1 p.Ser33fs (c.96del) is no gnomAD frequency available for this variant (gnomAD).

LARGE1 p.Ser33fs

c.96del · rs2520889050 · VCV2747160

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 2 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1

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.Ser33fs
Coding: c.96del
MANE Select: NM_133642
dbSNP: rs2520889050
Type: Deletion
Location: chr22:33761381 (GRCh38)
Gene constraint: LOEUF 0.606 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.15 · 4 PDB

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.Ser33= Conflicting classifications of pathogenicity ★ same residue
LARGE1 c.788-5_826del Likely pathogenic ★ same condition
LARGE1 p.Glu207fs Pathogenic ★ same condition
LARGE1 p.Glu63fs Pathogenic ★ same condition
LARGE1 p.Leu567fs Pathogenic ★ same condition
LARGE1 p.Leu604fs Pathogenic ★ same condition
LARGE1 p.Phe162fs Likely pathogenic ★ same condition
LARGE1 p.Phe404fs Pathogenic ★ 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-ser33fs (accessed [today's date]).

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