Is DYNC2H1 p.Phe3378fs (c.10134del) pathogenic?

DYNC2H1 p.Phe3378fs (c.10134del) is classified Pathogenic in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). Very rare (popmax 0.00017%, nfe); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Phe3378fs (c.10134del)?

DYNC2H1 p.Phe3378fs (c.10134del) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Phe3378fs (c.10134del) in the general population?

DYNC2H1 p.Phe3378fs (c.10134del) is very rare (popmax 0.00017%, nfe) (gnomAD).

DYNC2H1 p.Phe3378fs

c.10134del · VCV3677905

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 66 of 89
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,520 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,276 alleles · very rare exomes 2/1,461,134 · genomes 0/152,142 · joint denominator

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: DYNC2H1
Protein: p.Phe3378fs
Coding: c.10134del
MANE Select: NM_001377
Type: Deletion
Location: chr11:103253373 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3378: the 'aaa 5' 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.Phe3378= Likely benign ★ same residue
DYNC2H1 c.1360+2del Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 p.Arg1881fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 p.Asn1495fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 p.Asp4156fs Pathogenic ★★ same condition
DYNC2H1 p.Gln1566fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 p.Glu1949fs Pathogenic ★★ same condition
DYNC2H1 p.His1896fs 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/dync2h1-p-phe3378fs (accessed [today's date]).

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