Is COL6A2 p.Phe997fs (c.2988dup) pathogenic?

COL6A2 p.Phe997fs (c.2988dup) is classified Pathogenic in COL6A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-15). Absent from gnomAD; Associated with Bethlem myopathy 1A.

What condition is associated with COL6A2 p.Phe997fs (c.2988dup)?

COL6A2 p.Phe997fs (c.2988dup) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A2 p.Phe997fs (c.2988dup) in the general population?

COL6A2 p.Phe997fs (c.2988dup) is absent from gnomAD (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.Phe997fs

c.2988dup · rs1555877364 · VCV476481

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Bethlem myopathy 1A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (28 of 28) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL6A2
Protein: p.Phe997fs
Coding: c.2988dup
MANE Select: NM_001849
dbSNP: rs1555877364
Type: Duplication
Location: chr21:46132479 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 1 PDB
Residue 997: the vwfa 3 domain; the 'nonhelical region' region; a β-strand

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.Phe997Leu Uncertain significance ★ ⚠ same residue
COL6A2 p.Phe997= Likely benign ★ same residue
COL6A2 p.Asn771Lysfs Pathogenic/Likely pathogenic ★★ same condition
COL6A2 p.Gln889fs Pathogenic/Likely pathogenic ★★ same condition
COL6A2 c.1817-2dup Uncertain significance ★★ same condition
COL6A2 c.801+2dup Uncertain significance ★★ same condition
COL6A2 p.Ala860_Arg861insGlnGlnValAla Uncertain significance ★★ same condition
COL6A2 p.Asp949_Thr952dup Uncertain significance ★★ 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-phe997fs (accessed [today's date]).

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