Is DAG1 p.Gln673Pro (c.2018A>C) pathogenic?

DAG1 p.Gln673Pro (c.2018A>C) is classified Uncertain significance in DAG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-16). AlphaMissense: likely benign (0.2949); Very rare (popmax 0.00333%, amr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2P.

What condition is associated with DAG1 p.Gln673Pro (c.2018A>C)?

DAG1 p.Gln673Pro (c.2018A>C) 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.Gln673Pro (c.2018A>C) in the general population?

DAG1 p.Gln673Pro (c.2018A>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about DAG1 p.Gln673Pro (c.2018A>C)?

AlphaMissense predicts likely benign (score 0.2949) — an in-silico prediction, not a clinical call.

DAG1 p.Gln673Pro

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.2018A>C · rs1433049354 · VCV1450953

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2949 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2P

Computational evidence

Protein change
AlphaMissense	0.2949	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -10.40	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,883 bp · p 0.0007 · regional, not allelic
Overall
CADD	22.7	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 0.00333% Admixed American · 2/60,034 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,702 alleles · very rare

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.Gln673Pro
Coding: c.2018A>C
MANE Select: NM_004393
dbSNP: rs1433049354
Type: single nucleotide variant
Location: chr3:49532529 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 673: an α-helix; a disulfide bond; the peptidase s72 domain

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.Gln673Arg 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-gln673pro (accessed [today's date]).

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