Is COL6A2 p.Phe73= (c.219C>T) pathogenic?

COL6A2 p.Phe73= (c.219C>T) is classified Conflicting classifications of pathogenicity in COL6A2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-12-20). Rare (popmax 0.291%, sas); Associated with collagen 6-related myopathy.

What condition is associated with COL6A2 p.Phe73= (c.219C>T)?

COL6A2 p.Phe73= (c.219C>T) is associated with collagen 6-related myopathy, Bethlem myopathy 1A (ClinVar).

How common is COL6A2 p.Phe73= (c.219C>T) in the general population?

COL6A2 p.Phe73= (c.219C>T) is rare (popmax 0.291%, sas) (gnomAD).

COL6A2 p.Phe73=

c.219C>T · rs374336669 · VCV286220

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.291%, sas)

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 -6.3	GERP -3.3
Overall
CADD	8.477	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.291% South Asian · 265/91,076 alleles

Filtering AF 0.262% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.251%

Overall 0.0205% 330/1,613,180 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.291%	344
Remaining individualsnot grpmax-eligible	0.0352%	2,841
African / African-American	0.0173%	5,772
East Asian	0.00446%	22,435
Admixed American	0.00333%	30,012
European (non-Finnish)	0.0022%	45,386

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: COL6A2
Protein: p.Phe73=
Coding: c.219C>T
MANE Select: NM_001849
dbSNP: rs374336669
Type: single nucleotide variant
Location: chr21:46112082 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 1 PDB
Residue 73: the vwfa 1 domain; the 'nonhelical region' region

Full COL6A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: Bethlem myopathy 1A

Similar variants

COL6A2 p.Phe73Leu Uncertain significance ★ ⚠ same residue
COL6A2 p.Phe73Cys Uncertain significance ★ ⚠ same residue
COL6A2 c.1000-1G>T Pathogenic ★★ same condition
COL6A2 c.1000-2A>C Pathogenic ★★ same condition
COL6A2 c.1053+1G>A Pathogenic ★★ same condition
COL6A2 c.1053+1G>C Pathogenic/Likely pathogenic ★★ same condition
COL6A2 c.1053+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL6A2 c.1054-2A>G 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/col6a2-p-phe73 (accessed [today's date]).

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