Is DYNC2I2 p.Arg373fs (c.1117_1118del) pathogenic?

DYNC2I2 p.Arg373fs (c.11171118del) is classified Pathogenic in DYNC2I2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). Absent from gnomAD; Associated with short-rib thoracic dysplasia 11 with or without polydactyly.

What condition is associated with DYNC2I2 p.Arg373fs (c.1117_1118del)?

DYNC2I2 p.Arg373fs (c.1117_1118del) is associated with short-rib thoracic dysplasia 11 with or without polydactyly (ClinVar).

How common is DYNC2I2 p.Arg373fs (c.1117_1118del) in the general population?

DYNC2I2 p.Arg373fs (c.1117_1118del) is absent from gnomAD (gnomAD).

DYNC2I2 p.Arg373fs

c.1117_1118del · rs2542431260 · VCV2057434

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 7 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.1	GERP -0.65, phastCons 0.003

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DYNC2I2
Protein: p.Arg373fs
Coding: c.1117_1118del
MANE Select: NM_052844
dbSNP: rs2542431260
Type: Microsatellite
Location: chr9:128634785 (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.Arg373Leu Uncertain significance ★★ ⚠ same residue
DYNC2I2 p.Arg373Trp Uncertain significance ★★ ⚠ same residue
DYNC2I2 p.Glu368fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Thr473fs Likely pathogenic ★ same condition
DYNC2I2 p.Thr514fs Likely pathogenic ★ same condition
DYNC2I2 p.Val398fs Pathogenic ★ same condition
DYNC2I2 p.Gln144dup Uncertain significance ★ same condition
DYNC2I2 c.1373-12CT[2] Likely benign ★ 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-arg373fs (accessed [today's date]).

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