Is DYNC2I2 p.Glu368fs (c.1103_1104del) pathogenic?

DYNC2I2 p.Glu368fs (c.11031104del) is classified Pathogenic/Likely pathogenic in DYNC2I2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-26). Ultra-rare (popmax 0.0156%, nfe); Associated with short-rib thoracic dysplasia 11 with or without polydactyly.

What condition is associated with DYNC2I2 p.Glu368fs (c.1103_1104del)?

DYNC2I2 p.Glu368fs (c.1103_1104del) is associated with short-rib thoracic dysplasia 11 with or without polydactyly (ClinVar).

How common is DYNC2I2 p.Glu368fs (c.1103_1104del) in the general population?

DYNC2I2 p.Glu368fs (c.1103_1104del) is ultra-rare (popmax 0.0156%, nfe) (gnomAD).

DYNC2I2 p.Glu368fs

c.1103_1104del · rs759150616 · VCV838321

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, 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 7 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP -0.64, phastCons 0.77
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% European (non-Finnish) · 184/1,179,560 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.013%

Overall 0.0123% 199/1,612,442 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0156%	6,411
Finnishnot grpmax-eligible	0.0142%	7,046
African / African-American	0.00534%	18,730
Remaining individualsnot grpmax-eligible	0.0032%	31,211

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.Glu368fs
Coding: c.1103_1104del
MANE Select: NM_052844
dbSNP: rs759150616
Type: Microsatellite
Location: chr9:128634799 (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.Arg373fs 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
DYNC2I2 c.1372+1G>A Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Arg121Ter 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-glu368fs (accessed [today's date]).

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