Is DYNC2I1 p.Gln89fs (c.265_268del) pathogenic?

DYNC2I1 p.Gln89fs (c.265268del) is classified Likely pathogenic in DYNC2I1 (ClinVar, Single submitter, 1 submitter). Associated with short-rib thoracic dysplasia 8 with or without polydactyly.

What condition is associated with DYNC2I1 p.Gln89fs (c.265_268del)?

DYNC2I1 p.Gln89fs (c.265_268del) is associated with short-rib thoracic dysplasia 8 with or without polydactyly (ClinVar).

DYNC2I1 p.Gln89fs

c.265_268del · VCV3906974

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

short-rib thoracic dysplasia 8 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 3 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.5	GERP -1.7

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

Variant & gene context

Gene: DYNC2I1
Protein: p.Gln89fs
Coding: c.265_268del
MANE Select: NM_018051
Type: Microsatellite
Location: chr7:158871330 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.87 · 4 PDB
Residue 89: the 'disordered' region

Full DYNC2I1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 8 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2I1 p.Gln89= Likely benign ★ same residue
DYNC2I1 p.Asp175_Ser176insTer Pathogenic ★ same condition
DYNC2I1 p.Glu238fs Pathogenic ★ same condition
DYNC2I1 p.Ile885fs Pathogenic ★ same condition
DYNC2I1 p.Glu263del Uncertain significance ★ same condition
DYNC2I1 p.Ser646del Uncertain significance ★ same condition
DYNC2I1 p.Arg228Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2I1 p.Arg441Ter 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/dync2i1-p-gln89fs (accessed [today's date]).

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