Is DYNC2H1 p.Pro2869fs (c.8604dup) pathogenic?

DYNC2H1 p.Pro2869fs (c.8604dup) is classified Likely pathogenic in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-05). Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2H1 p.Pro2869fs (c.8604dup)?

DYNC2H1 p.Pro2869fs (c.8604dup) is associated with asphyxiating thoracic dystrophy 3 (ClinVar).

DYNC2H1 p.Pro2869fs

c.8604dup · VCV3598890

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

asphyxiating thoracic dystrophy 3

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 54 of 89
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: DYNC2H1
Protein: p.Pro2869fs
Coding: c.8604dup
MANE Select: NM_001377
Type: Duplication
Location: chr11:103211852 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2869: an α-helix

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

Disease context

asphyxiating thoracic dystrophy 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2H1 p.Ala681fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 p.Asn3797fs Likely pathogenic ★★ same condition
DYNC2H1 p.Asp3856fs 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 p.Ala1816fs Likely pathogenic ★ same condition
DYNC2H1 p.Ala2674fs Likely 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-pro2869fs (accessed [today's date]).

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