Is DAG1 p.Phe241fs (c.721_722del) pathogenic?

DAG1 p.Phe241fs (c.721722del) is classified Likely pathogenic in DAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-11). Absent from gnomAD; Associated with autosomal recessive limb-girdle muscular dystrophy type 2P.

What condition is associated with DAG1 p.Phe241fs (c.721_722del)?

DAG1 p.Phe241fs (c.721_722del) is associated with autosomal recessive limb-girdle muscular dystrophy type 2P (ClinVar).

How common is DAG1 p.Phe241fs (c.721_722del) in the general population?

DAG1 p.Phe241fs (c.721_722del) is absent from gnomAD (gnomAD).

DAG1 p.Phe241fs

Q: How is Alpha-dystroglycan-related limb-girdle muscular dystrophy R16 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.721_722del · rs2472606199 · VCV1709072

Likely pathogenic Single submitter

Classification

Likely 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

autosomal recessive limb-girdle muscular dystrophy type 2P

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.6	GERP -4.1, 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: DAG1
Protein: p.Phe241fs
Coding: c.721_722del
MANE Select: NM_004393
dbSNP: rs2472606199
Type: Deletion
Location: chr3:49531232 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 241: a disulfide bond; the 'required for laminin recognition' region; a β-strand

Full DAG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2P — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Alpha-dystroglycan-related limb-girdle muscular dystrophy R16 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

DAG1 c.286-10del Benign/Likely benign ★★ same condition
DAG1 p.Gln147fs Pathogenic ★ same condition
DAG1 p.Gln206fs Pathogenic ★ same condition
DAG1 p.Phe152fs Likely pathogenic ★ same condition
DAG1 c.286-1_287del Uncertain significance ★ same condition
DAG1 p.317TP[1] Uncertain significance ★ same condition
DAG1 p.Arg454fs Uncertain significance ★ same condition
DAG1 p.Arg489fs 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/dag1-p-phe241fs (accessed [today's date]).

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