Is COL6A2 p.Phe883= (c.2649C>T) pathogenic?

COL6A2 p.Phe883= (c.2649C>T) is classified Likely benign in COL6A2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-06-01). Rare (popmax 0.933%, nfe); Associated with Ullrich congenital muscular dystrophy 1A.

What condition is associated with COL6A2 p.Phe883= (c.2649C>T)?

COL6A2 p.Phe883= (c.2649C>T) is associated with Ullrich congenital muscular dystrophy 1A, myosclerosis, Bethlem myopathy 1A (ClinVar).

How common is COL6A2 p.Phe883= (c.2649C>T) in the general population?

COL6A2 p.Phe883= (c.2649C>T) is rare (popmax 0.933%, nfe) (gnomAD).

How is Ullrich congenital muscular dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

COL6A2 p.Phe883=

c.2649C>T · rs149172490 · VCV262302

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.933%, nfe)

Conditions

Ullrich congenital muscular dystrophy 1A

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 -0.33	GERP -2.6, phastCons 0.15
Overall
CADD	17.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.933% European (non-Finnish) · 11,008/1,179,930 alleles

Filtering AF 0.918% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.912%

Overall 0.744% 12,000/1,613,024 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.933%	107
Remaining individualsnot grpmax-eligible	0.544%	184
Ashkenazi Jewishnot grpmax-eligible	0.504%	198
Admixed American	0.378%	264
African / African-American	0.172%	582
Finnishnot grpmax-eligible	0.17%	589
Middle Eastern	0.115%	866
South Asian	0.0296%	3,373
East Asian	0.0134%	7,479

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.Phe883=
Coding: c.2649C>T
MANE Select: NM_001849 · reported on NM_058174
dbSNP: rs149172490
Type: single nucleotide variant
Location: chr21:46129383 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 1 PDB
Residue 883: the vwfa 3 domain; the 'nonhelical region' region

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

Disease context

Ullrich congenital muscular dystrophy 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myosclerosis Bethlem myopathy 1A

For Ullrich congenital muscular dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (United Kingdom)

Similar variants

COL6A2 p.Gly883Asp 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
COL6A2 c.115+2T>C 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-phe883 (accessed [today's date]).

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