Is DNAH8 p.Met4465fs (c.13394del) pathogenic?

DNAH8 p.Met4465fs (c.13394del) is classified Pathogenic in DNAH8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). Very rare (popmax 0.00168%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Met4465fs (c.13394del)?

DNAH8 p.Met4465fs (c.13394del) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH8 p.Met4465fs (c.13394del) in the general population?

DNAH8 p.Met4465fs (c.13394del) is very rare (popmax 0.00168%, amr) (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.Met4465fs

c.13394del · rs2534078747 · VCV2801918

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

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 90 of 93
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% Admixed American · 1/59,562 alleles

Overall 6.86e-05% 1/1,456,972 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: DNAH8
Protein: p.Met4465fs
Coding: c.13394del
MANE Select: NM_001206927
dbSNP: rs2534078747
Type: Deletion
Location: chr6:39012237 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)
Residue 4465: 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.Gly3905fs Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.His2321fs Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.Thr1162fs Pathogenic/Likely pathogenic ★★ same condition
DNAH8 c.10141-4del Benign ★★ same condition
DNAH8 c.762+8del Likely benign ★★ same condition
DNAH8 c.7620+15del Benign/Likely benign ★★ same condition
DNAH8 p.Ala2943fs Pathogenic ★ same condition
DNAH8 p.Ala3537fs 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-met4465fs (accessed [today's date]).

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