Is DNAAF5 p.Phe255fs (c.763_766del) pathogenic?

DNAAF5 p.Phe255fs (c.763766del) is classified Pathogenic in DNAAF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-25). Very rare (popmax 8.47e-05%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF5 p.Phe255fs (c.763_766del)?

DNAAF5 p.Phe255fs (c.763_766del) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF5 p.Phe255fs (c.763_766del) in the general population?

DNAAF5 p.Phe255fs (c.763_766del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DNAAF5 p.Phe255fs

c.763_766del · rs2484024185 · VCV2728813

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, 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 2 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 1.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.84e-05% 1/1,461,848 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: DNAAF5
Protein: p.Phe255fs
Coding: c.763_766del
MANE Select: NM_017802
dbSNP: rs2484024185
Type: Deletion
Location: chr7:729828 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.80

Full DNAAF5 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

DNAAF5 c.2082+8del Benign/Likely benign ★★ same condition
DNAAF5 p.Ala122fs Pathogenic ★ same condition
DNAAF5 p.Ala764fs Pathogenic ★ same condition
DNAAF5 p.Arg83fs Pathogenic ★ same condition
DNAAF5 p.Asn320fs Pathogenic ★ same condition
DNAAF5 p.Gly271fs Pathogenic ★ same condition
DNAAF5 p.His163fs Pathogenic ★ same condition
DNAAF5 p.His236fs 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/dnaaf5-p-phe255fs (accessed [today's date]).

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