Is DYNC2I2 p.Val398fs (c.1193_1194del) pathogenic?

DYNC2I2 p.Val398fs (c.11931194del) is classified Pathogenic in DYNC2I2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-24). Very rare (popmax 0.00116%, sas); Associated with short-rib thoracic dysplasia 11 with or without polydactyly.

What condition is associated with DYNC2I2 p.Val398fs (c.1193_1194del)?

DYNC2I2 p.Val398fs (c.1193_1194del) is associated with short-rib thoracic dysplasia 11 with or without polydactyly (ClinVar).

How common is DYNC2I2 p.Val398fs (c.1193_1194del) in the general population?

DYNC2I2 p.Val398fs (c.1193_1194del) is very rare (popmax 0.00116%, sas) (gnomAD).

DYNC2I2 p.Val398fs

c.1193_1194del · VCV4532118

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00116%, sas)

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 7.8	GERP 1.5, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00116% South Asian · 1/86,274 alleles

Overall 0.00021% 3/1,425,554 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00164%	60,994
South Asiangrpmax	0.00116%	86,274
European (non-Finnish)	8.61e-05%	1,161,946

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val398fs
Coding: c.1193_1194del
MANE Select: NM_052844
Type: Microsatellite
Location: chr9:128634709 (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.Glu368fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Arg373fs Pathogenic ★ same condition
DYNC2I2 p.Thr473fs Likely pathogenic ★ same condition
DYNC2I2 p.Thr514fs Likely 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-val398fs (accessed [today's date]).

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