Is DYNC2H1 p.Leu403fs (c.1206dup) pathogenic?

DYNC2H1 p.Leu403fs (c.1206dup) is classified Pathogenic in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-22). Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Leu403fs (c.1206dup)?

DYNC2H1 p.Leu403fs (c.1206dup) is associated with Jeune syndrome (ClinVar).

DYNC2H1 p.Leu403fs

c.1206dup · VCV3642555

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Jeune syndrome

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 89
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 2.2, phastCons 1

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

Variant & gene context

Gene: DYNC2H1
Protein: p.Leu403fs
Coding: c.1206dup
MANE Select: NM_001377
Type: Duplication
Location: chr11:103120756 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 403: the 'stem' region

Full DYNC2H1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Jeune syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2H1 p.Leu403= Likely benign ★ same residue
DYNC2H1 p.Ala681fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 p.Gln4161fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 p.Ile1088fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 p.Ile3610fs Pathogenic ★★ same condition
DYNC2H1 c.10043-16dup Likely benign ★★ same condition
DYNC2H1 c.10043-7dup Benign/Likely benign ★★ same condition
DYNC2H1 c.11257-11dup Benign/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/dync2h1-p-leu403fs (accessed [today's date]).

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