Is DNAH1 p.Arg159fs (c.475del) pathogenic?

DNAH1 p.Arg159fs (c.475del) is classified Pathogenic in DNAH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-18). Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Arg159fs (c.475del)?

DNAH1 p.Arg159fs (c.475del) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

DNAH1 p.Arg159fs

c.475del · VCV3759819

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

spermatogenic failure 18

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 4 of 78
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.2	GERP 5.9, phastCons 1

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

Variant & gene context

Gene: DNAH1
Protein: p.Arg159fs
Coding: c.475del
MANE Select: NM_015512
Type: Deletion
Location: chr3:52326206 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 159: the 'stem' region

Full DNAH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ciliary dyskinesia, primary, 37

Similar variants

DNAH1 p.Arg159Trp Uncertain significance ★★ ⚠ same residue
DNAH1 p.Arg159Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
DNAH1 p.Ala4048fs Pathogenic/Likely pathogenic ★★ same condition
DNAH1 p.Asn648fs Pathogenic/Likely pathogenic ★★ same condition
DNAH1 p.Pro3909fs Pathogenic ★★ same condition
DNAH1 p.Val2559fs Pathogenic/Likely pathogenic ★★ same condition
DNAH1 c.6526-10_6526-9del Benign/Likely benign ★★ same condition
DNAH1 c.6666+14del 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/dnah1-p-arg159fs (accessed [today's date]).

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