Is COL6A2 p.Ser823= (c.2469C>T) pathogenic?

COL6A2 p.Ser823= (c.2469C>T) is classified Likely benign in COL6A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-19). Very rare (popmax 0.00558%, sas); Associated with Bethlem myopathy 1A.

What condition is associated with COL6A2 p.Ser823= (c.2469C>T)?

COL6A2 p.Ser823= (c.2469C>T) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A2 p.Ser823= (c.2469C>T) in the general population?

COL6A2 p.Ser823= (c.2469C>T) is very rare (popmax 0.00558%, sas) (gnomAD).

How is Bethlem muscular dystrophy inherited?

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

COL6A2 p.Ser823=

c.2469C>T · VCV4711644

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00558%, sas)

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 -0.77	GERP -2.6, phastCons 0.009
Overall
CADD	5.031	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00558% South Asian · 5/89,568 alleles

Filtering AF 0.00213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.00144% 23/1,602,532 alleles · very rare exomes 21/1,450,294 · genomes 2/152,238 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00558%	17,914
Finnishnot grpmax-eligible	0.00334%	29,952
African / African-American	0.00268%	37,327
East Asian	0.00226%	44,238
Admixed American	0.00169%	59,258
European (non-Finnish)	0.00102%	98,047

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.Ser823=
Coding: c.2469C>T
MANE Select: NM_001849
Type: single nucleotide variant
Location: chr21:46131961 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 1 PDB
Residue 823: the 'nonhelical region' region

Full COL6A2 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

COL6A2 p.Ser823Thr Uncertain significance ★ ⚠ same residue
COL6A2 p.Pro823Thr Likely benign ★★ same residue
COL6A2 p.Pro823= Likely benign ★ 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

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-ser823 (accessed [today's date]).

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