Is COL11A2 p.Ala407fs (c.1218dup) pathogenic?

COL11A2 p.Ala407fs (c.1218dup) is classified Likely pathogenic in COL11A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). Associated with autosomal dominant nonsyndromic hearing loss 13.

What condition is associated with COL11A2 p.Ala407fs (c.1218dup)?

COL11A2 p.Ala407fs (c.1218dup) is associated with autosomal dominant nonsyndromic hearing loss 13 (ClinVar).

COL11A2 p.Ala407fs

c.1218dup · VCV3572968

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autosomal dominant nonsyndromic hearing loss 13

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 10 of 66
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 0.77, phastCons 1

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

Variant & gene context

Gene: COL11A2
Protein: p.Ala407fs
Coding: c.1218dup
MANE Select: NM_080680
Type: Duplication
Location: chr6:33180966 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 407: the 'nonhelical region' region; the 'disordered' region; the collagen-like 1 domain

Full COL11A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant nonsyndromic hearing loss 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL11A2 p.Ala407Val Uncertain significance ★★ ⚠ same residue
COL11A2 p.Gly1111fs Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Ser864fs Likely pathogenic ★ same condition
COL11A2 p.Ala407= Conflicting classifications of pathogenicity ★ same residue
COL11A2 p.Ala407Glu Uncertain significance ★ ⚠ same residue
COL11A2 c.1819-2A>G Likely pathogenic ★★ same condition
COL11A2 c.3852+1G>T Likely pathogenic ★★ same condition
COL11A2 p.Arg1020Ter Pathogenic/Likely 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/col11a2-p-ala407fs (accessed [today's date]).

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