Is DNAH1 p.Ala976fs (c.2926del) pathogenic?

DNAH1 p.Ala976fs (c.2926del) is classified Pathogenic in DNAH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-05). Very rare (popmax 8.48e-05%, nfe); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Ala976fs (c.2926del)?

DNAH1 p.Ala976fs (c.2926del) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Ala976fs (c.2926del) in the general population?

DNAH1 p.Ala976fs (c.2926del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

DNAH1 p.Ala976fs

c.2926del · rs2471187488 · VCV2002471

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 18 of 78
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.6	GERP -1.7

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) · 1/1,179,646 alleles

Overall 6.84e-05% 1/1,461,366 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.Ala976fs
Coding: c.2926del
MANE Select: NM_015512
dbSNP: rs2471187488
Type: Deletion
Location: chr3:52352606 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 976: the 'stem' region; 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: ciliary dyskinesia, primary, 37

Similar variants

DNAH1 p.Ala976Thr 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
DNAH1 c.1435_1444+3del 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-ala976fs (accessed [today's date]).

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