Is DYNC2H1 p.Ser4041Ter (c.12122delinsGATTGAGG) pathogenic?

DYNC2H1 p.Ser4041Ter (c.12122delinsGATTGAGG) is classified Pathogenic in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2H1 p.Ser4041Ter (c.12122delinsGATTGAGG)?

DYNC2H1 p.Ser4041Ter (c.12122delinsGATTGAGG) is associated with asphyxiating thoracic dystrophy 3 (ClinVar).

DYNC2H1 p.Ser4041Ter

c.12122delinsGATTGAGG · VCV4081638

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 83 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.

Variant & gene context

Gene: DYNC2H1
Protein: p.Ser4041Ter
Coding: c.12122delinsGATTGAGG
MANE Select: NM_001377
Type: Indel
Location: chr11:103358325 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4041: 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.Tyr2715_Gln2716delinsTer Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 p.Gly1396Ter Likely pathogenic ★ same condition
DYNC2H1 p.Gly46fs Likely pathogenic ★ same condition
DYNC2H1 p.Trp860Ter Likely pathogenic ★ same condition
DYNC2H1 p.Ser4041Cys Uncertain significance ★ same residue
DYNC2H1 c.10042+2T>G Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 c.10462-2A>G Likely pathogenic ★★ same condition
DYNC2H1 c.10606-14A>G Pathogenic/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-ser4041ter (accessed [today's date]).

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