Is COL6A3 p.Lys2103= (c.6309G>A) pathogenic?

COL6A3 p.Lys2103= (c.6309G>A) is classified Pathogenic in COL6A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-24). Absent from gnomAD v4.1; Associated with Bethlem myopathy 1A.

What condition is associated with COL6A3 p.Lys2103= (c.6309G>A)?

COL6A3 p.Lys2103= (c.6309G>A) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A3 p.Lys2103= (c.6309G>A) in the general population?

COL6A3 p.Lys2103= (c.6309G>A) is absent from gnomAD v4.1 (gnomAD).

How is Bethlem muscular dystrophy inherited?

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

COL6A3 p.Lys2103=

c.6309G>A · rs1574975196 · VCV659368

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Bethlem myopathy 1A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.67	acceptor loss, 26 bp away · masked 0 · deltas
Pangolin	Δ0.67	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL6A3
Protein: p.Lys2103=
Coding: c.6309G>A
MANE Select: NM_004369
dbSNP: rs1574975196
Type: single nucleotide variant
Location: chr2:237359362 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 2103: the 'triple-helical region' region; the 'disordered' region; a modified residue (5-hydroxylysine; alternate)

Full COL6A3 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

COL6A3 p.Lys2103Asn Conflicting classifications of pathogenicity ★ same residue
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
COL6A3 c.6309+1G>A Pathogenic ★★ same condition
COL6A3 c.6309+1G>T 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/col6a3-p-lys2103 (accessed [today's date]).

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