Is DAG1 p.Ser567= (c.1701C>T) pathogenic?

DAG1 p.Ser567= (c.1701C>T) is classified Benign in DAG1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.48%, afr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2P.

What condition is associated with DAG1 p.Ser567= (c.1701C>T)?

DAG1 p.Ser567= (c.1701C>T) 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.Ser567= (c.1701C>T) in the general population?

DAG1 p.Ser567= (c.1701C>T) is low-frequency (popmax 1.48%, afr) (gnomAD).

DAG1 p.Ser567=

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.1701C>T · rs142579425 · VCV257586

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.48%, afr)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2P

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 0.019	GERP -0.014, phastCons 0.79
Overall
CADD	4.512	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.48% African / African-American · 1,111/75,054 alleles

Filtering AF 1.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.38%

Overall 0.0822% 1,327/1,614,118 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.48%	68
Middle Eastern	0.214%	466
Admixed American	0.143%	698
Remaining individualsnot grpmax-eligible	0.123%	812
South Asian	0.011%	9,108
European (non-Finnish)	0.00254%	39,331

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.Ser567=
Coding: c.1701C>T
MANE Select: NM_004393
dbSNP: rs142579425
Type: single nucleotide variant
Location: chr3:49532212 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 567: an α-helix

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.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-ser567 (accessed [today's date]).

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