Is DAG1 p.Val73= (c.219C>T) pathogenic?

DAG1 p.Val73= (c.219C>T) is classified Conflicting classifications of pathogenicity in DAG1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-14). Rare (popmax 0.479%, eas); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9.

How common is DAG1 p.Val73= (c.219C>T) in the general population?

DAG1 p.Val73= (c.219C>T) is rare (popmax 0.479%, eas) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

DAG1 p.Val73=

Q: What condition is associated with DAG1 p.Val73= (c.219C>T)?

DAG1 p.Val73= (c.219C>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.219C>T · rs145165301 · VCV500026

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.479%, eas)

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 -5.3	GERP -3.4
Overall
CADD	4.988	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.479% East Asian · 215/44,882 alleles

Filtering AF 0.426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.406%

Overall 0.0159% 257/1,614,186 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.479%	209
Remaining individualsnot grpmax-eligible	0.0128%	7,814
Admixed American	0.00666%	15,008
African / African-American	0.00267%	37,518
European (non-Finnish)	0.00229%	43,705
Finnishnot grpmax-eligible	0.00156%	64,020

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.Val73=
Coding: c.219C>T
MANE Select: NM_004393
dbSNP: rs145165301
Type: single nucleotide variant
Location: chr3:49510753 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 73: 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.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
DAG1 p.Ala610Val 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-val73 (accessed [today's date]).

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