Is COL6A3 p.Phe61Ter (c.181_182insAG) pathogenic?

COL6A3 p.Phe61Ter (c.181182insAG) is classified Pathogenic in COL6A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-07). Very rare (popmax 0.000593%, nfe); Associated with Bethlem myopathy 1A.

What condition is associated with COL6A3 p.Phe61Ter (c.181_182insAG)?

COL6A3 p.Phe61Ter (c.181_182insAG) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A3 p.Phe61Ter (c.181_182insAG) in the general population?

COL6A3 p.Phe61Ter (c.181_182insAG) is very rare (popmax 0.000593%, nfe) (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.Phe61Ter

c.181_182insAG · rs1559280064 · VCV2063517

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

Bethlem myopathy 1A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 44
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,180,018 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,461,758 alleles · very rare

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: COL6A3
Protein: p.Phe61Ter
Coding: c.181_182insAG
MANE Select: NM_004369
dbSNP: rs1559280064
Type: Insertion
Location: chr2:237395114 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 61: the vwfa 1 domain; the 'nonhelical region' region

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.Phe61Val Uncertain significance ★ same residue
COL6A3 p.Phe61Ser Likely benign ★ same residue
COL6A3 p.Lys2976_Pro2977insAlaAlaAlaThrLysProAlaLys Uncertain significance ★ same condition
COL6A3 p.Phe61Leu Uncertain significance ★ ⚠ same residue
COL6A3 c.6063+13_6063+14insTA Likely benign ★ same condition
COL6A3 c.6063+14_6063+15insG Likely benign ★ same condition
COL6A3 c.5838+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL6A3 c.6156+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/col6a3-p-phe61ter (accessed [today's date]).

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