Is DAG1 p.Asp111= (c.333C>T) pathogenic?

DAG1 p.Asp111= (c.333C>T) is classified Likely benign in DAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). Very rare (popmax 0.00102%, nfe); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9.

How common is DAG1 p.Asp111= (c.333C>T) in the general population?

DAG1 p.Asp111= (c.333C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

DAG1 p.Asp111=

Q: What condition is associated with DAG1 p.Asp111= (c.333C>T)?

DAG1 p.Asp111= (c.333C>T) is associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9, autosomal recessive limb-girdle muscular dystrophy type 2P (ClinVar).

c.333C>T · rs1221719616 · VCV1147257

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9

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 -0.37	GERP -2
Overall
CADD	0.666	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,180,014 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000821% 12/1,461,882 alleles · very rare

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: DAG1
Protein: p.Asp111=
Coding: c.333C>T
MANE Select: NM_004393
dbSNP: rs1221719616
Type: single nucleotide variant
Location: chr3:49530844 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 111: a UniProt-annotated variant site (in mddgc9; does not affect dystroglycan expression; impairs alpha-dystroglycan glycosylation); 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

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2P

For Walker-Warburg syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (United Kingdom)

Similar variants

DAG1 p.Asp111Asn Benign/Likely benign ★★ ⚠ same residue
DAG1 p.Ser14Ter Pathogenic ★★ same condition
DAG1 p.Trp110Ter Pathogenic/Likely pathogenic ★★ same condition
DAG1 p.Ala135Ser Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala135Thr Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala279Ser Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala285Thr Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala285Val 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-asp111 (accessed [today's date]).

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