Is COL6A1 p.Pro358= (c.1074T>C) pathogenic?

COL6A1 p.Pro358= (c.1074T>C) is classified Likely benign in COL6A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-06). Absent from gnomAD v4.1; Associated with Bethlem myopathy 1A.

What condition is associated with COL6A1 p.Pro358= (c.1074T>C)?

COL6A1 p.Pro358= (c.1074T>C) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A1 p.Pro358= (c.1074T>C) in the general population?

COL6A1 p.Pro358= (c.1074T>C) 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.

COL6A1 p.Pro358=

c.1074T>C · rs2123473427 · VCV1088851

Likely benign Single submitter

Classification

Likely benign

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 carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.3
Overall
CADD	0.02	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: COL6A1
Protein: p.Pro358=
Coding: c.1074T>C
MANE Select: NM_001848
dbSNP: rs2123473427
Type: single nucleotide variant
Location: chr21:45990996 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 358: the 'disordered' region; the 'triple-helical region' region

Full COL6A1 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

COL6A1 p.Pro358Leu Uncertain significance ★ ⚠ same residue
COL6A1 p.Pro358Ser Uncertain significance ★ ⚠ same residue
COL6A1 c.1002+1G>A Pathogenic ★★ same condition
COL6A1 c.1003-1G>A Pathogenic ★★ same condition
COL6A1 c.1003-2A>C Pathogenic ★★ same condition
COL6A1 c.1003-2A>G Pathogenic ★★ same condition
COL6A1 c.1056+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL6A1 c.1056+1G>C 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/col6a1-p-pro358 (accessed [today's date]).

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