Is DYNC2I2 p.Leu438fs (c.1312_1313del) pathogenic?

DYNC2I2 p.Leu438fs (c.13121313del) is classified Pathogenic/Likely pathogenic in DYNC2I2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-09-06). Very rare (popmax 0.00534%, afr); Associated with DYNC2I2 & WDR34-related disorders.

What condition is associated with DYNC2I2 p.Leu438fs (c.1312_1313del)?

DYNC2I2 p.Leu438fs (c.1312_1313del) is associated with DYNC2I2 & WDR34-related disorders, short-rib thoracic dysplasia 11 with or without polydactyly (ClinVar).

How common is DYNC2I2 p.Leu438fs (c.1312_1313del) in the general population?

DYNC2I2 p.Leu438fs (c.1312_1313del) is very rare (popmax 0.00534%, afr) (gnomAD).

DYNC2I2 p.Leu438fs

c.1312_1313del · rs753802842 · VCV665979

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

DYNC2I2 & WDR34-related disorders

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 8 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.8	GERP -0.6, phastCons 1
Overall
CADD	34.0	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 0.00534% African / African-American · 4/74,932 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00273% 44/1,613,768 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,733
European (non-Finnish)	0.00331%	30,256
South Asian	0.0011%	91,094

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.Leu438fs
Coding: c.1312_1313del
MANE Select: NM_052844
dbSNP: rs753802842
Type: Deletion
Location: chr9:128634285 (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

DYNC2I2 & WDR34-related disorders

Also linked: short-rib thoracic dysplasia 11 with or without polydactyly

Similar variants

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
DYNC2I2 p.Gln504_Gly505insTer Pathogenic ★ same condition
DYNC2I2 p.Gln86fs Pathogenic ★ same condition
DYNC2I2 p.Glu116fs 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-leu438fs (accessed [today's date]).

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