Is DNAH5 p.Arg2170fs (c.6508dup) pathogenic?

DNAH5 p.Arg2170fs (c.6508dup) is classified Pathogenic/Likely pathogenic in DNAH5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-21). Very rare (popmax 0.00398%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Arg2170fs (c.6508dup)?

DNAH5 p.Arg2170fs (c.6508dup) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 3 (ClinVar).

How common is DNAH5 p.Arg2170fs (c.6508dup) in the general population?

DNAH5 p.Arg2170fs (c.6508dup) is very rare (popmax 0.00398%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DNAH5 p.Arg2170fs

c.6508dup · rs878854458 · VCV238983

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00398%, nfe)

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 39 of 79
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Overall
CADD	35.0	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 0.00398% European (non-Finnish) · 47/1,179,984 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00297% 48/1,613,980 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00398%	25,106
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: DNAH5
Protein: p.Arg2170fs
Coding: c.6508dup
MANE Select: NM_001369
dbSNP: rs878854458
Type: Duplication
Location: chr5:13824269 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

Full DNAH5 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

Also linked: primary ciliary dyskinesia 3

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

DNAH5 p.Arg2170= Likely benign ★ same residue
DNAH5 p.Arg2639fs Pathogenic ★★ same condition
DNAH5 p.Arg293fs Pathogenic/Likely pathogenic ★★ same condition
DNAH5 p.Asn4487Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH5 p.Cys3400fs Pathogenic/Likely pathogenic ★★ same condition
DNAH5 p.Glu3093fs Pathogenic/Likely pathogenic ★★ same condition
DNAH5 p.Glu3537fs Pathogenic/Likely pathogenic ★★ same condition
DNAH5 p.Glu3979fs Pathogenic/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/dnah5-p-arg2170fs (accessed [today's date]).

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