Is COL6A2 p.Arg720= (c.2160C>G) pathogenic?

COL6A2 p.Arg720= (c.2160C>G) is classified Benign/Likely benign in COL6A2 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-02). Common (popmax 6.29%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Bethlem myopathy 1A.

What condition is associated with COL6A2 p.Arg720= (c.2160C>G)?

COL6A2 p.Arg720= (c.2160C>G) is associated with Bethlem myopathy 1A, Ullrich congenital muscular dystrophy 1A, myosclerosis (ClinVar).

How is Bethlem muscular dystrophy inherited?

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

COL6A2 p.Arg720=

Q: How common is COL6A2 p.Arg720= (c.2160C>G) in the general population?

COL6A2 p.Arg720= (c.2160C>G) is common (popmax 6.29%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2160C>G · rs61735829 · VCV93934

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 6.29%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Bethlem myopathy 1A

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 -0.55	GERP -2.6, phastCons 0.015
Overall
CADD	7.484	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.29% African / African-American · 4,720/75,008 alleles

Filtering AF 6.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.08%

Overall 0.332% 5,358/1,613,124 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.29%	16
Admixed American	0.466%	214
Remaining individualsnot grpmax-eligible	0.41%	244
Middle Eastern	0.215%	466
South Asian	0.00878%	11,385
European (non-Finnish)	0.00686%	14,567

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: COL6A2
Protein: p.Arg720=
Coding: c.2160C>G
MANE Select: NM_001849
dbSNP: rs61735829
Type: single nucleotide variant
Location: chr21:46125975 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 1 PDB
Residue 720: the vwfa 2 domain; the 'nonhelical region' region

Full COL6A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bethlem myopathy 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ullrich congenital muscular dystrophy 1A myosclerosis collagen 6-related myopathy

For Bethlem muscular dystrophy (Orphanet):

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

Similar variants

COL6A2 p.Arg720Cys Uncertain significance ★★ ⚠ same residue
COL6A2 p.Arg720His Uncertain significance ★★ ⚠ same residue
COL6A2 c.1000-1G>T Pathogenic ★★ same condition
COL6A2 c.1000-2A>C Pathogenic ★★ same condition
COL6A2 c.1053+1G>A Pathogenic ★★ same condition
COL6A2 c.1053+1G>C Pathogenic/Likely pathogenic ★★ same condition
COL6A2 c.1053+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL6A2 c.1054-2A>G Pathogenic/Likely 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/col6a2-p-arg720 (accessed [today's date]).

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