Is COL6A2 p.Lys966= (c.2898G>A) pathogenic?

COL6A2 p.Lys966= (c.2898G>A) is classified Likely benign in COL6A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-04). Very rare (popmax 0.00446%, eas); Associated with Bethlem myopathy 1A.

What condition is associated with COL6A2 p.Lys966= (c.2898G>A)?

COL6A2 p.Lys966= (c.2898G>A) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A2 p.Lys966= (c.2898G>A) in the general population?

COL6A2 p.Lys966= (c.2898G>A) is very rare (popmax 0.00446%, 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.Lys966=

c.2898G>A · rs759502409 · VCV512473

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, 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 4.4	GERP -0.65, phastCons 1
Overall
CADD	7.406	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,836 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00124% 18/1,457,180 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,418
Remaining individualsnot grpmax-eligible	0.0032%	31,208
European (non-Finnish)	0.00119%	84,234

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.Lys966=
Coding: c.2898G>A
MANE Select: NM_001849
dbSNP: rs759502409
Type: single nucleotide variant
Location: chr21:46132390 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 1 PDB
Residue 966: the vwfa 3 domain; an α-helix; 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

For Bethlem muscular dystrophy (Orphanet):

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

Similar variants

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
COL6A2 c.115+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL6A2 c.1180-1G>A 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-lys966 (accessed [today's date]).

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