Is COL6A1 p.Pro555= (c.1665C>T) pathogenic?

COL6A1 p.Pro555= (c.1665C>T) is classified Conflicting classifications of pathogenicity in COL6A1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-17). Ultra-rare (popmax 0.0321%, nfe); Associated with collagen 6-related myopathy.

What condition is associated with COL6A1 p.Pro555= (c.1665C>T)?

COL6A1 p.Pro555= (c.1665C>T) is associated with collagen 6-related myopathy, Bethlem myopathy 1A (ClinVar).

How common is COL6A1 p.Pro555= (c.1665C>T) in the general population?

COL6A1 p.Pro555= (c.1665C>T) is ultra-rare (popmax 0.0321%, nfe) (gnomAD).

COL6A1 p.Pro555=

c.1665C>T · rs369802454 · VCV93825

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0321%, nfe)

Conditions

collagen 6-related myopathy

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 -3.1
Overall
CADD	2.485	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0321% European (non-Finnish) · 369/1,148,314 alleles

Filtering AF 0.0294% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0284%

Overall 0.0252% 391/1,553,940 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0321%	3,112
Remaining individualsnot grpmax-eligible	0.0183%	5,473
African / African-American	0.00815%	12,265
East Asian	0.00239%	41,780
South Asian	0.00237%	42,175
Admixed American	0.00196%	51,148
Finnishnot grpmax-eligible	0.0017%	58,978

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: COL6A1
Protein: p.Pro555=
Coding: c.1665C>T
MANE Select: NM_001848
dbSNP: rs369802454
Type: single nucleotide variant
Location: chr21:45998950 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 555: the 'disordered' region; the 'triple-helical region' region

Full COL6A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: Bethlem myopathy 1A

Similar variants

COL6A1 p.Pro555_Asp557dup 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
COL6A1 c.1056+2T>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/col6a1-p-pro555 (accessed [today's date]).

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