Is COL6A3 p.Ala1617Ser (c.4849G>T) pathogenic?

COL6A3 p.Ala1617Ser (c.4849G>T) is classified Uncertain significance in COL6A3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-20). AlphaMissense: likely benign (0.0804); Absent from gnomAD v4.1; Associated with Bethlem myopathy 1A.

What condition is associated with COL6A3 p.Ala1617Ser (c.4849G>T)?

COL6A3 p.Ala1617Ser (c.4849G>T) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A3 p.Ala1617Ser (c.4849G>T) in the general population?

COL6A3 p.Ala1617Ser (c.4849G>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.Ala1617Ser (c.4849G>T)?

AlphaMissense predicts likely benign (score 0.0804) — an in-silico prediction, not a clinical call.

COL6A3 p.Ala1617Ser

c.4849G>T · rs200433282 · VCV595829

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0804 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Bethlem myopathy 1A

Computational evidence

Protein change
AlphaMissense	0.0804	likely benign
REVEL	0.192	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.081	GERP -0.57
Regional constraint	o/e 1.01	unconstrained · MANE · 6,991 bp · p 0.73 · regional, not allelic
Overall
CADD	6.681	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

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.Ala1617Ser
Coding: c.4849G>T
MANE Select: NM_004369
dbSNP: rs200433282
Type: single nucleotide variant
Location: chr2:237368614 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 1617: the 'nonhelical region' region; the 'disordered' 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.Ala1617Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
COL6A3 p.Ala1617Val 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-ala1617ser (accessed [today's date]).

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