Is DAG1 p.Arg779Gln (c.2336G>A) pathogenic?

DAG1 p.Arg779Gln (c.2336G>A) is classified Uncertain significance in DAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-08). AlphaMissense: likely pathogenic (0.818); Very rare (popmax 0.00133%, afr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2P.

What condition is associated with DAG1 p.Arg779Gln (c.2336G>A)?

DAG1 p.Arg779Gln (c.2336G>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2P, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 (ClinVar).

How common is DAG1 p.Arg779Gln (c.2336G>A) in the general population?

DAG1 p.Arg779Gln (c.2336G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DAG1 p.Arg779Gln (c.2336G>A)?

AlphaMissense predicts likely pathogenic (score 0.818) — an in-silico prediction, not a clinical call.

DAG1 p.Arg779Gln

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.2336G>A · rs1283360967 · VCV660048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.818 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2P

Computational evidence

Protein change
AlphaMissense	0.818	likely pathogenic
REVEL	0.549	indeterminate
SaProt	LLR -7.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,883 bp · p 0.0007 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,928 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,613,952 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,928
South Asian	0.0011%	91,088
European (non-Finnish)	0.000254%	393,340

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.Arg779Gln
Coding: c.2336G>A
MANE Select: NM_004393
dbSNP: rs1283360967
Type: single nucleotide variant
Location: chr3:49532847 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB

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

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

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

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

DAG1 p.Arg779Trp 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
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-arg779gln (accessed [today's date]).

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