Is COL6A3 p.Arg609Ter (c.1825C>T) pathogenic?

COL6A3 p.Arg609Ter (c.1825C>T) is classified Pathogenic/Likely pathogenic in COL6A3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-10-01). Very rare (popmax 0.00167%, amr); Associated with Ullrich congenital muscular dystrophy 1C.

What condition is associated with COL6A3 p.Arg609Ter (c.1825C>T)?

COL6A3 p.Arg609Ter (c.1825C>T) is associated with Ullrich congenital muscular dystrophy 1C, Bethlem myopathy 1A (ClinVar).

How common is COL6A3 p.Arg609Ter (c.1825C>T) in the general population?

COL6A3 p.Arg609Ter (c.1825C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Ullrich congenital muscular dystrophy inherited?

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

COL6A3 p.Arg609Ter

c.1825C>T · rs755382829 · VCV857930

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Ullrich congenital muscular dystrophy 1C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 44
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.6, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,012 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000372% 6/1,614,074 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,012
African / African-American	0.00133%	74,936
European (non-Finnish)	0.000339%	295,011

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: COL6A3
Protein: p.Arg609Ter
Coding: c.1825C>T
MANE Select: NM_004369
dbSNP: rs755382829
Type: single nucleotide variant
Location: chr2:237380987 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 609: the 'nonhelical region' region; the vwfa 3 domain

Full COL6A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: Bethlem myopathy 1A

For Ullrich congenital muscular dystrophy (Orphanet):

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

Similar variants

COL6A3 p.Arg609Gln Conflicting classifications of pathogenicity ★ same residue
COL6A3 p.Arg609= Likely benign ★ same residue
COL6A3 c.3071-2A>G Likely pathogenic ★★ same condition
COL6A3 c.5838+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL6A3 c.6156+1G>A Pathogenic ★★ same condition
COL6A3 c.6157-2A>C Pathogenic ★★ same condition
COL6A3 c.6210+1G>A Pathogenic ★★ same condition
COL6A3 c.6282+1G>A 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/col6a3-p-arg609ter (accessed [today's date]).

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