Is COL6A3 p.Pro517= (c.1551C>G) pathogenic?

COL6A3 p.Pro517= (c.1551C>G) is classified Likely benign in COL6A3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-30). Ultra-rare (popmax 0.0461%, sas); Associated with collagen 6-related myopathy.

What condition is associated with COL6A3 p.Pro517= (c.1551C>G)?

COL6A3 p.Pro517= (c.1551C>G) is associated with collagen 6-related myopathy, Bethlem myopathy 1A (ClinVar).

How common is COL6A3 p.Pro517= (c.1551C>G) in the general population?

COL6A3 p.Pro517= (c.1551C>G) is ultra-rare (popmax 0.0461%, sas) (gnomAD).

COL6A3 p.Pro517=

c.1551C>G · rs764955459 · VCV899264

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0461%, sas)

Conditions

collagen 6-related myopathy

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 0.29	GERP -1.6, phastCons 0.032
Overall
CADD	4.744	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0461% South Asian · 42/91,088 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0311%

Overall 0.00273% 44/1,614,120 alleles · ultra-rare exomes 42/1,461,894 · genomes 2/152,226 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0461%	2,169
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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: COL6A3
Protein: p.Pro517=
Coding: c.1551C>G
MANE Select: NM_004369
dbSNP: rs764955459
Type: single nucleotide variant
Location: chr2:237381261 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 517: the 'nonhelical region' region; the vwfa 3 domain

Full COL6A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: Bethlem myopathy 1A

Similar variants

COL6A3 p.Pro517Thr 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.6282+1G>C Pathogenic/Likely 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-pro517 (accessed [today's date]).

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