Is DNAH8 p.Ala184fs (c.549dup) pathogenic?

DNAH8 p.Ala184fs (c.549dup) is classified Pathogenic in DNAH8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). Ultra-rare (popmax 0.0167%, mid); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Ala184fs (c.549dup)?

DNAH8 p.Ala184fs (c.549dup) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH8 p.Ala184fs (c.549dup) in the general population?

DNAH8 p.Ala184fs (c.549dup) is ultra-rare (popmax 0.0167%, mid) (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.Ala184fs

c.549dup · rs1032638497 · VCV2160631

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

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 4 of 93
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.49	GERP -4.9

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Middle Eastern · 1/6,002 alleles

Filtering AF 0.000906% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000451%

Overall 0.000911% 13/1,426,922 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	6,002
South Asian	0.00341%	29,311
Remaining individualsnot grpmax-eligible	0.00163%	61,302
European (non-Finnish)	0.000694%	144,169

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.Ala184fs
Coding: c.549dup
MANE Select: NM_001206927
dbSNP: rs1032638497
Type: Duplication
Location: chr6:38729918 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)

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.Ala184Val Conflicting classifications of pathogenicity ★ same residue
DNAH8 p.Ala184= Likely benign ★ same residue
DNAH8 p.Gly46_Asp53dup Uncertain significance ★★ same condition
DNAH8 c.6131+25dup Benign ★★ same condition
DNAH8 c.2395+1dup Pathogenic ★ same condition
DNAH8 p.Arg108fs Pathogenic ★ same condition
DNAH8 p.Asn3972fs Pathogenic ★ same condition
DNAH8 p.Asn619fs 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-ala184fs (accessed [today's date]).

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