Is DNAH8 p.Glu1012fs (c.3031_3034dup) pathogenic?

DNAH8 p.Glu1012fs (c.30313034dup) is classified Pathogenic in DNAH8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-16). Ultra-rare (gnomAD MAF 2.011e-05); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Glu1012fs (c.3031_3034dup)?

DNAH8 p.Glu1012fs (c.3031_3034dup) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH8 p.Glu1012fs (c.3031_3034dup) in the general population?

DNAH8 p.Glu1012fs (c.3031_3034dup) is ultra-rare (gnomAD MAF 2.011e-05) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DNAH8 p.Glu1012fs

c.3031_3034dup · rs781128315 · VCV2839971

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 2.011e-05)

Conditions

primary ciliary dyskinesia

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 22 of 93
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.9	GERP -3.6, phastCons 0.014

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

Population frequency

dbSNP / gnomAD

Global frequency 0.00201% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: DNAH8
Protein: p.Glu1012fs
Coding: c.3031_3034dup
MANE Select: NM_001206927
dbSNP: rs781128315
Type: Duplication
Location: chr6:38803304 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)
Residue 1012: a UniProt-annotated variant site (found in a patient with primary ciliary dyskinesia; uncertain significance)

Full DNAH8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DNAH8 p.Gly46_Asp53dup Uncertain significance ★★ same condition
DNAH8 c.6131+25dup Benign ★★ same condition
DNAH8 c.2395+1dup Pathogenic ★ same condition
DNAH8 p.Ala184fs Pathogenic ★ same condition
DNAH8 p.Arg108fs Pathogenic ★ same condition
DNAH8 p.Asn3972fs Pathogenic ★ same condition
DNAH8 p.Asn619fs Pathogenic ★ same condition
DNAH8 p.Asp2660fs 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/dnah8-p-glu1012fs (accessed [today's date]).

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