Is COL11A2 p.Pro972fs (c.2915del) pathogenic?

COL11A2 p.Pro972fs (c.2915del) is classified Pathogenic in COL11A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-16). Very rare (popmax 8.57e-05%, nfe).

How common is COL11A2 p.Pro972fs (c.2915del) in the general population?

COL11A2 p.Pro972fs (c.2915del) is very rare (popmax 8.57e-05%, nfe) (gnomAD).

COL11A2 p.Pro972fs

c.2915del · VCV4715229

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.57e-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 40 of 66
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -3.7

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.57e-05% European (non-Finnish) · 1/1,167,178 alleles

Overall 6.97e-05% 1/1,434,998 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: COL11A2
Protein: p.Pro972fs
Coding: c.2915del
MANE Select: NM_080680
Type: Deletion
Location: chr6:33172362 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 972: the 'disordered' region; the 'triple-helical region' region

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

Similar variants

COL11A2 p.Gly922fs Pathogenic ★★ same type
COL11A2 p.Ile1223fs Pathogenic/Likely pathogenic ★★ same type
COL11A2 p.Pro897fs Pathogenic/Likely pathogenic ★★ same type
COL11A2 p.Glu301del Uncertain significance ★★ same type
COL11A2 c.1359+17del Likely benign ★★ same type
COL11A2 c.1819-18_1819-9del Likely benign ★★ same type
COL11A2 c.2116-14_2116-10del Likely benign ★★ same type
COL11A2 c.2431-18del Benign ★★ 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/col11a2-p-pro972fs (accessed [today's date]).

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