Is DAG1 p.Pro889= (c.2667T>A) pathogenic?

DAG1 p.Pro889= (c.2667T>A) is classified Likely benign in DAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). Ultra-rare (popmax 0.01%, amr); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9.

How common is DAG1 p.Pro889= (c.2667T>A) in the general population?

DAG1 p.Pro889= (c.2667T>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

DAG1 p.Pro889=

Q: What condition is associated with DAG1 p.Pro889= (c.2667T>A)?

DAG1 p.Pro889= (c.2667T>A) is associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9, autosomal recessive limb-girdle muscular dystrophy type 2P (ClinVar).

c.2667T>A · rs760977919 · VCV702820

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

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 0.59	GERP -0.99, phastCons 1
Overall
CADD	8.577	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,994 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.0018% 29/1,613,310 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,999
South Asian	0.00549%	18,217
Remaining individualsnot grpmax-eligible	0.0032%	31,237
African / African-American	0.00134%	74,898
European (non-Finnish)	0.00127%	78,666

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.Pro889=
Coding: c.2667T>A
MANE Select: NM_004393
dbSNP: rs760977919
Type: single nucleotide variant
Location: chr3:49533178 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 889: an α-helix; the 'required for interaction with cav3' region; the 'disordered' region; the 'required for binding dmd and utrn' region

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-pro889 (accessed [today's date]).

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