Is COL6A1 p.Asp548fs (c.1641_1642del) pathogenic?

COL6A1 p.Asp548fs (c.16411642del) is classified Pathogenic in COL6A1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-19). Absent from gnomAD; Associated with Ullrich congenital muscular dystrophy 1A.

What condition is associated with COL6A1 p.Asp548fs (c.1641_1642del)?

COL6A1 p.Asp548fs (c.1641_1642del) is associated with Ullrich congenital muscular dystrophy 1A (ClinVar).

How common is COL6A1 p.Asp548fs (c.1641_1642del) in the general population?

COL6A1 p.Asp548fs (c.1641_1642del) is absent from gnomAD (gnomAD).

How is Ullrich congenital muscular dystrophy inherited?

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

COL6A1 p.Asp548fs

c.1641_1642del · rs1569518771 · VCV595434

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Ullrich congenital muscular dystrophy 1A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 25 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL6A1
Protein: p.Asp548fs
Coding: c.1641_1642del
MANE Select: NM_001848
dbSNP: rs1569518771
Type: Deletion
Location: chr21:45998923 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 548: the 'disordered' region; the 'triple-helical region' region

Full COL6A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ullrich congenital muscular dystrophy 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Ullrich congenital muscular dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (United Kingdom)

Similar variants

COL6A1 p.Lys185fs Pathogenic ★★ same condition
COL6A1 p.Lys310del Pathogenic/Likely pathogenic ★★ same condition
COL6A1 p.Asp548= Benign/Likely benign ★★ same residue
COL6A1 c.1006del Pathogenic ★ same condition
COL6A1 p.Gln735fs Pathogenic ★ same condition
COL6A1 c.1002+6_1002+88del Likely benign ★ same condition
COL6A1 p.Asp548Asn Benign ★ ⚠ same residue
COL6A1 p.Ala489fs Pathogenic 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/col6a1-p-asp548fs (accessed [today's date]).

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