Is COL6A3 p.Pro2817Ser (c.8449C>T) pathogenic?

COL6A3 p.Pro2817Ser (c.8449C>T) is classified Uncertain significance in COL6A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-26). AlphaMissense: ambiguous (0.457); Absent from gnomAD v4.1; Associated with Bethlem myopathy 1A.

What condition is associated with COL6A3 p.Pro2817Ser (c.8449C>T)?

COL6A3 p.Pro2817Ser (c.8449C>T) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A3 p.Pro2817Ser (c.8449C>T) in the general population?

COL6A3 p.Pro2817Ser (c.8449C>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 COL6A3 p.Pro2817Ser (c.8449C>T)?

AlphaMissense predicts ambiguous (score 0.457) — an in-silico prediction, not a clinical call.

COL6A3 p.Pro2817Ser

c.8449C>T · rs2076962218 · VCV2140839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.457 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Bethlem myopathy 1A

Computational evidence

Protein change
AlphaMissense	0.457	ambiguous
REVEL	0.575	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 34 kb · p 0.074 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL6A3
Protein: p.Pro2817Ser
Coding: c.8449C>T
MANE Select: NM_004369
dbSNP: rs2076962218
Type: single nucleotide variant
Location: chr2:237340467 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 2817: an α-helix; the 'nonhelical region' region

Full COL6A3 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

COL6A3 p.Pro2817= Benign/Likely benign ★★ same residue
COL6A3 p.Pro2817Leu Uncertain significance ★ same residue
COL6A3 c.5838+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL6A3 c.6156+1G>A Pathogenic ★★ same condition
COL6A3 c.6157-2A>C Pathogenic ★★ same condition
COL6A3 c.6210+1G>A Pathogenic ★★ same condition
COL6A3 c.6282+1G>A Pathogenic ★★ same condition
COL6A3 c.6309+1G>A 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/col6a3-p-pro2817ser (accessed [today's date]).

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