Is DNAH5 p.Ala4354fs (c.13060del) pathogenic?

DNAH5 p.Ala4354fs (c.13060del) is classified Pathogenic/Likely pathogenic in DNAH5 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-07-29). Very rare (popmax 0.00167%, amr); Associated with primary ciliary dyskinesia 3.

What condition is associated with DNAH5 p.Ala4354fs (c.13060del)?

DNAH5 p.Ala4354fs (c.13060del) is associated with primary ciliary dyskinesia 3, primary ciliary dyskinesia (ClinVar).

How common is DNAH5 p.Ala4354fs (c.13060del) in the general population?

DNAH5 p.Ala4354fs (c.13060del) is very rare (popmax 0.00167%, amr) (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.Ala4354fs

c.13060del · rs1370489117 · VCV568028

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

primary ciliary dyskinesia 3

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 75 of 79
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP 0.85, phastCons 0.99
Overall
CADD	24.4	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 0.00167% Admixed American · 1/60,010 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000929% 15/1,613,984 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,010
European (non-Finnish)	0.00119%	84,286

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.Ala4354fs
Coding: c.13060del
MANE Select: NM_001369
dbSNP: rs1370489117
Type: Deletion
Location: chr5:13714470 (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 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

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.Ala4354= Benign/Likely benign ★★ same residue
DNAH5 p.Ala4354Ser Likely benign ★ same residue
DNAH5 p.Ala4354Val Likely benign ★ same residue
DNAH5 c.2577+2del Likely pathogenic ★★ same condition
DNAH5 c.54_57+5del Likely pathogenic ★★ same condition
DNAH5 c.7609+1_7609+3del Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.9605+1del Pathogenic/Likely pathogenic ★★ same condition
DNAH5 p.Ala1977fs 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-ala4354fs (accessed [today's date]).

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