Is DNAH1 p.Pro68fs (c.202_203del) pathogenic?

DNAH1 p.Pro68fs (c.202203del) is classified Pathogenic in DNAH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-05). Very rare (popmax 8.48e-05%, nfe); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Pro68fs (c.202_203del)?

DNAH1 p.Pro68fs (c.202_203del) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Pro68fs (c.202_203del) in the general population?

DNAH1 p.Pro68fs (c.202_203del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

DNAH1 p.Pro68fs

c.202_203del · rs2471123795 · VCV2029087

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 2 of 78
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.21	GERP -3.8

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,846 alleles

Overall 6.84e-05% 1/1,461,662 alleles · very rare

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: DNAH1
Protein: p.Pro68fs
Coding: c.202_203del
MANE Select: NM_015512
dbSNP: rs2471123795
Type: Deletion
Location: chr3:52322642 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 68: the 'stem' region; the 'disordered' 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.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
DNAH1 c.1435_1444+3del Likely pathogenic ★ same condition
DNAH1 c.2728_2729+2del 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/dnah1-p-pro68fs (accessed [today's date]).

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