Is COL6A2 p.Pro471fs (c.1412del) pathogenic?

COL6A2 p.Pro471fs (c.1412del) is classified Likely pathogenic in COL6A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-03). Very rare (popmax 8.47e-05%, nfe).

How common is COL6A2 p.Pro471fs (c.1412del) in the general population?

COL6A2 p.Pro471fs (c.1412del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

COL6A2 p.Pro471fs

c.1412del · VCV4852723

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 17 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.29	GERP -2.9, phastCons 0.8

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,954 alleles

Overall 6.85e-05% 1/1,460,530 alleles · very rare

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.Pro471fs
Coding: c.1412del
MANE Select: NM_001849
Type: Deletion
Location: chr21:46121076 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 1 PDB
Residue 471: the 'triple-helical region' region; the 'disordered' region

Full COL6A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL6A2 p.Pro471Ser Uncertain significance ★ ⚠ same residue
COL6A2 c.1770+1del Pathogenic/Likely pathogenic ★★ same type
COL6A2 c.1817-3_1817-2del Likely pathogenic ★★ same type
COL6A2 c.955-2del Pathogenic ★★ same type
COL6A2 p.Gly277fs Pathogenic ★★ same type
COL6A2 p.Ile834fs Pathogenic/Likely pathogenic ★★ same type
COL6A2 p.Pro584fs Pathogenic ★★ same type
COL6A2 p.Ser488fs Pathogenic/Likely 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/col6a2-p-pro471fs (accessed [today's date]).

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