Is DAG1 p.Phe635= (c.1905C>T) pathogenic?

DAG1 p.Phe635= (c.1905C>T) is classified Conflicting classifications of pathogenicity in DAG1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-21). Ultra-rare (popmax 0.0329%, sas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2P.

What condition is associated with DAG1 p.Phe635= (c.1905C>T)?

DAG1 p.Phe635= (c.1905C>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.Phe635= (c.1905C>T) in the general population?

DAG1 p.Phe635= (c.1905C>T) is ultra-rare (popmax 0.0329%, sas) (gnomAD).

DAG1 p.Phe635=

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.1905C>T · rs577609846 · VCV282414

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, sas)

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 -3.9	GERP -4.1
Overall
CADD	2.031	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% South Asian · 30/91,080 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.00452% 73/1,614,214 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0329%	3,036
Finnishnot grpmax-eligible	0.0109%	9,146
Remaining individualsnot grpmax-eligible	0.0064%	15,628
European (non-Finnish)	0.00254%	39,335
Admixed American	0.00167%	60,036
African / African-American	0.00133%	75,058

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.Phe635=
Coding: c.1905C>T
MANE Select: NM_004393
dbSNP: rs577609846
Type: single nucleotide variant
Location: chr3:49532416 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 635: an α-helix; 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.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-phe635 (accessed [today's date]).

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