Is DAG1 p.His161Asp (c.481C>G) pathogenic?

DAG1 p.His161Asp (c.481C>G) is classified Uncertain significance in DAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). AlphaMissense: likely benign (0.1173); Absent from gnomAD v4.1; Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9.

How common is DAG1 p.His161Asp (c.481C>G) in the general population?

DAG1 p.His161Asp (c.481C>G) is absent from gnomAD v4.1 (gnomAD).

How is Walker-Warburg syndrome inherited?

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

What do computational predictors say about DAG1 p.His161Asp (c.481C>G)?

AlphaMissense predicts likely benign (score 0.1173) — an in-silico prediction, not a clinical call.

DAG1 p.His161Asp

Q: What condition is associated with DAG1 p.His161Asp (c.481C>G)?

DAG1 p.His161Asp (c.481C>G) is associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9, autosomal recessive limb-girdle muscular dystrophy type 2P (ClinVar).

c.481C>G · rs2051326372 · VCV1046703

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1173 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.1173	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -4.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 21 kb · p 0.0053 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DAG1
Protein: p.His161Asp
Coding: c.481C>G
MANE Select: NM_004393
dbSNP: rs2051326372
Type: single nucleotide variant
Location: chr3:49530992 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 161: the 'required for laminin recognition' region; an α-helix

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.His161= Likely benign ★ same residue
DAG1 p.His161fs Uncertain significance ★ 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

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-his161asp (accessed [today's date]).

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