Is DYNC2I2 p.Pro9fs (c.26del) pathogenic?

DYNC2I2 p.Pro9fs (c.26del) is classified Pathogenic in DYNC2I2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-06). Very rare (popmax 0.000448%, nfe); Associated with short-rib thoracic dysplasia 11 with or without polydactyly.

What condition is associated with DYNC2I2 p.Pro9fs (c.26del)?

DYNC2I2 p.Pro9fs (c.26del) is associated with short-rib thoracic dysplasia 11 with or without polydactyly (ClinVar).

How common is DYNC2I2 p.Pro9fs (c.26del) in the general population?

DYNC2I2 p.Pro9fs (c.26del) is very rare (popmax 0.000448%, nfe) (gnomAD).

DYNC2I2 p.Pro9fs

c.26del · rs763975565 · VCV576613

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000448%, nfe)

Conditions

short-rib thoracic dysplasia 11 with or without polydactyly

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 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.5	GERP -4.2

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000448% European (non-Finnish) · 5/1,115,528 alleles

Filtering AF 0.000131% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.5e-05%

Overall 0.000384% 5/1,303,064 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: DYNC2I2
Protein: p.Pro9fs
Coding: c.26del
MANE Select: NM_052844
dbSNP: rs763975565
Type: Deletion
Location: chr9:128656701 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.66 · 4 PDB

Full DYNC2I2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 11 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2I2 p.Pro9Gln Uncertain significance ★ ⚠ same residue
DYNC2I2 p.Pro9= Likely benign ★ same residue
DYNC2I2 p.Leu438fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Phe439fs Pathogenic ★★ same condition
DYNC2I2 p.Pro210fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Pro32fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 c.1372+5del Uncertain significance ★★ same condition
DYNC2I2 c.546-1_547del 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/dync2i2-p-pro9fs (accessed [today's date]).

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