Is COL6A1 p.Phe631= (c.1893C>T) pathogenic?

COL6A1 p.Phe631= (c.1893C>T) is classified Likely benign in COL6A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-25). Ultra-rare (popmax 0.0187%, afr); Associated with Bethlem myopathy 1A.

What condition is associated with COL6A1 p.Phe631= (c.1893C>T)?

COL6A1 p.Phe631= (c.1893C>T) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A1 p.Phe631= (c.1893C>T) in the general population?

COL6A1 p.Phe631= (c.1893C>T) is ultra-rare (popmax 0.0187%, afr) (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.Phe631=

c.1893C>T · rs374031718 · VCV1102714

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Conditions

Bethlem myopathy 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 -9.4	GERP -3.5
Overall
CADD	8.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/75,038 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00903%

Overall 0.00174% 28/1,612,826 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,360
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.016%	6,248
Admixed American	0.00167%	60,026
South Asian	0.0011%	91,088
European (non-Finnish)	8.48e-05%	1,179,896

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.Phe631=
Coding: c.1893C>T
MANE Select: NM_001848
dbSNP: rs374031718
Type: single nucleotide variant
Location: chr21:46001323 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 631: the vwfa 2 domain; the 'c-terminal globular domain' 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 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
COL6A1 c.1056+5G>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-phe631 (accessed [today's date]).

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