Is COL6A1 p.Ala28Val (c.83C>T) pathogenic?

COL6A1 p.Ala28Val (c.83C>T) is classified Uncertain significance in COL6A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely benign (0.082); Absent from gnomAD v4.1; Associated with Bethlem myopathy 1A.

What condition is associated with COL6A1 p.Ala28Val (c.83C>T)?

COL6A1 p.Ala28Val (c.83C>T) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A1 p.Ala28Val (c.83C>T) in the general population?

COL6A1 p.Ala28Val (c.83C>T) is absent from gnomAD v4.1 (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.Ala28Val (c.83C>T)?

AlphaMissense predicts likely benign (score 0.082) — an in-silico prediction, not a clinical call.

COL6A1 p.Ala28Val

c.83C>T · rs2526305516 · VCV1939892

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.082 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,606,870)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bethlem myopathy 1A

Computational evidence

Protein change
AlphaMissense	0.082	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -1.1, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 8,412 bp · p 0.26 · regional, not allelic
Overall
CADD	13.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,606,870). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL6A1
Protein: p.Ala28Val
Coding: c.83C>T
MANE Select: NM_001848
dbSNP: rs2526305516
Type: single nucleotide variant
Location: chr21:45981933 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 28: the 'n-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-ala28val (accessed [today's date]).

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