Is COL6A1 p.Pro349fs (c.1042_1043dup) pathogenic?

COL6A1 p.Pro349fs (c.10421043dup) is classified Likely pathogenic in COL6A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-18). Absent from gnomAD.

How common is COL6A1 p.Pro349fs (c.1042_1043dup) in the general population?

COL6A1 p.Pro349fs (c.1042_1043dup) is absent from gnomAD (gnomAD).

COL6A1 p.Pro349fs

c.1042_1043dup · rs2123473129 · VCV1324133

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Pro349fs
Coding: c.1042_1043dup
MANE Select: NM_001848
dbSNP: rs2123473129
Type: Duplication
Location: chr21:45990810 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 349: the 'disordered' region; the 'triple-helical region' region

Full COL6A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL6A1 p.Pro349= Likely benign ★★ same residue
COL6A1 c.1056+2dup Pathogenic ★★ same type
COL6A1 p.Glu24fs Pathogenic ★★ same type
COL6A1 c.1461+41dup Benign ★★ same type
COL6A1 c.588+19dup Benign ★★ same type
COL6A1 c.19dup Likely pathogenic ★ same type
COL6A1 p.Ala778fs Pathogenic ★ same type
COL6A1 p.Asn721fs Pathogenic ★ same type

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-pro349fs (accessed [today's date]).

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