Is COL6A2 p.Lys372= (c.1116G>A) pathogenic?

COL6A2 p.Lys372= (c.1116G>A) is classified Uncertain significance in COL6A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-09). Ultra-rare (popmax 0.0143%, sas); Associated with Bethlem myopathy 1A.

What condition is associated with COL6A2 p.Lys372= (c.1116G>A)?

COL6A2 p.Lys372= (c.1116G>A) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A2 p.Lys372= (c.1116G>A) in the general population?

COL6A2 p.Lys372= (c.1116G>A) is ultra-rare (popmax 0.0143%, sas) (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.Lys372=

c.1116G>A · rs762160379 · VCV850470

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

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 12	GERP 1.6, phastCons 1
Overall
CADD	19.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0143% South Asian · 13/90,836 alleles

Filtering AF 0.00846% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00663%

Overall 0.00105% 17/1,612,186 alleles · ultra-rare exomes 17/1,460,070 · genomes 0/152,116 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	6,987
East Asian	0.00892%	11,205

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.Lys372=
Coding: c.1116G>A
MANE Select: NM_001849
dbSNP: rs762160379
Type: single nucleotide variant
Location: chr21:46117936 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 1 PDB
Residue 372: 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 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-lys372 (accessed [today's date]).

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