Is DNAH1 p.Pro3909fs (c.11726_11727del) pathogenic?

DNAH1 p.Pro3909fs (c.1172611727del) is classified Pathogenic in DNAH1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-29). Ultra-rare (popmax 0.0803%, eas); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Pro3909fs (c.11726_11727del)?

DNAH1 p.Pro3909fs (c.11726_11727del) is associated with spermatogenic failure 18, primary ciliary dyskinesia, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Pro3909fs (c.11726_11727del) in the general population?

DNAH1 p.Pro3909fs (c.11726_11727del) is ultra-rare (popmax 0.0803%, eas) (gnomAD).

DNAH1 p.Pro3909fs

c.11726_11727del · rs779490893 · VCV430860

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0803%, eas)

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 73 of 78
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.2	GERP 0.34, phastCons 0.53
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0803% East Asian · 36/44,842 alleles

Filtering AF 0.0595% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00254% 41/1,612,970 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0803%	1,246
Remaining individualsnot grpmax-eligible	0.0016%	62,462
Finnishnot grpmax-eligible	0.00157%	63,590
African / African-American	0.00133%	75,006
European (non-Finnish)	0.00017%	589,817

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.Pro3909fs
Coding: c.11726_11727del
MANE Select: NM_015512
dbSNP: rs779490893
Type: Deletion
Location: chr3:52396983 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 3909: a UniProt-annotated variant site (in spgf18)

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: primary ciliary dyskinesia ciliary dyskinesia, primary, 37

Similar variants

DNAH1 p.Pro3909= Likely benign ★ same residue
DNAH1 p.Ala4048fs Pathogenic/Likely pathogenic ★★ same condition
DNAH1 p.Asn648fs Pathogenic/Likely 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-pro3909fs (accessed [today's date]).

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