Is COL6A2 p.Arg417= (c.1251C>G) pathogenic?

COL6A2 p.Arg417= (c.1251C>G) is classified Likely benign in COL6A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-30). Ultra-rare (popmax 0.0424%, eas); Associated with Bethlem myopathy 1A.

What condition is associated with COL6A2 p.Arg417= (c.1251C>G)?

COL6A2 p.Arg417= (c.1251C>G) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A2 p.Arg417= (c.1251C>G) in the general population?

COL6A2 p.Arg417= (c.1251C>G) is ultra-rare (popmax 0.0424%, eas) (gnomAD).

How is Bethlem muscular dystrophy inherited?

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

COL6A2 p.Arg417=

c.1251C>G · rs61735827 · VCV1607625

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0424%, eas)

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 -6.5	GERP -2.7
Overall
CADD	0.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0424% East Asian · 19/44,830 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.00279% 45/1,611,828 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0424%	2,359
Remaining individualsnot grpmax-eligible	0.0273%	3,669
African / African-American	0.0107%	9,360
European (non-Finnish)	8.48e-05%	1,179,682

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.Arg417=
Coding: c.1251C>G
MANE Select: NM_001849
dbSNP: rs61735827
Type: single nucleotide variant
Location: chr21:46119101 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 1 PDB
Residue 417: the 'triple-helical region' region; the 'disordered' 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

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.Arg417Leu Uncertain significance ★★ ⚠ same residue
COL6A2 p.Arg417Gly Uncertain significance ★ ⚠ same residue
COL6A2 p.Arg417His Conflicting classifications of pathogenicity ★ ⚠ same residue
COL6A2 p.Arg417fs Pathogenic ★ same residue
COL6A2 p.Arg417Cys 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

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-arg417 (accessed [today's date]).

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