Is COL6A1 p.Pro483Ser (c.1447C>T) pathogenic?

COL6A1 p.Pro483Ser (c.1447C>T) is classified Conflicting classifications of pathogenicity in COL6A1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0809); Ultra-rare (popmax 0.0133%, amr); Associated with Bethlem myopathy 1A.

What condition is associated with COL6A1 p.Pro483Ser (c.1447C>T)?

COL6A1 p.Pro483Ser (c.1447C>T) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A1 p.Pro483Ser (c.1447C>T) in the general population?

COL6A1 p.Pro483Ser (c.1447C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

How is Bethlem muscular dystrophy inherited?

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

What do computational predictors say about COL6A1 p.Pro483Ser (c.1447C>T)?

AlphaMissense predicts likely benign (score 0.0809) — an in-silico prediction, not a clinical call.

COL6A1 p.Pro483Ser

c.1447C>T · rs756017426 · VCV655411

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0809 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bethlem myopathy 1A

Computational evidence

Protein change
AlphaMissense	0.0809	likely benign
REVEL	0.402	indeterminate
SaProt	LLR -7.39	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/59,928 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000682% 11/1,611,988 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,491
Remaining individualsnot grpmax-eligible	0.0048%	20,824

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.Pro483Ser
Coding: c.1447C>T
MANE Select: NM_001848
dbSNP: rs756017426
Type: single nucleotide variant
Location: chr21:45997469 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 483: 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 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-pro483ser (accessed [today's date]).

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