Is DNAAF3 p.Ser54fs (c.161_162del) pathogenic?

DNAAF3 p.Ser54fs (c.161162del) is classified Pathogenic in DNAAF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-20). Very rare (popmax 0.00195%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF3 p.Ser54fs (c.161_162del)?

DNAAF3 p.Ser54fs (c.161_162del) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF3 p.Ser54fs (c.161_162del) in the general population?

DNAAF3 p.Ser54fs (c.161_162del) is very rare (popmax 0.00195%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DNAAF3 p.Ser54fs

c.161_162del · rs780701843 · VCV1322752

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00195%, 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 3 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.7	GERP 1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% European (non-Finnish) · 23/1,180,046 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00157% 23/1,461,886 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: DNAAF3
Protein: p.Ser54fs
Coding: c.161_162del
MANE Select: NM_001256715
dbSNP: rs780701843
Type: Microsatellite
Location: chr19:55165924 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.06

Full DNAAF3 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

DNAAF3 p.Ser54= Likely benign ★★ same residue
DNAAF3 p.Leu370fs Pathogenic ★ same condition
DNAAF3 p.Val55fs Conflicting classifications of pathogenicity ★ same condition
DNAAF3 c.1048+12ACA[2] Likely benign ★ same condition
DNAAF3 c.323-11TC[2] Likely benign ★ same condition
DNAAF3 c.789+1G>C Likely pathogenic ★★ same condition
DNAAF3 p.Ala399fs Pathogenic/Likely pathogenic ★★ same condition
DNAAF3 p.Arg205fs 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/dnaaf3-p-ser54fs (accessed [today's date]).

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