Is DNAAF2 p.Pro217fs (c.650del) pathogenic?

DNAAF2 p.Pro217fs (c.650del) is classified Pathogenic in DNAAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). Very rare (popmax 0.00511%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF2 p.Pro217fs (c.650del)?

DNAAF2 p.Pro217fs (c.650del) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF2 p.Pro217fs (c.650del) in the general population?

DNAAF2 p.Pro217fs (c.650del) is very rare (popmax 0.00511%, amr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DNAAF2 p.Pro217fs

c.650del · rs1566513076 · VCV2135585

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00511%, amr)

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 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.9	GERP -3.4

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00511% Admixed American · 3/58,754 alleles

Filtering AF 0.00136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000676%

Overall 0.000208% 3/1,442,044 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: DNAAF2
Protein: p.Pro217fs
Coding: c.650del
MANE Select: NM_018139
dbSNP: rs1566513076
Type: Deletion
Location: chr14:49634500 (GRCh38)
Gene constraint: LOEUF 1.811 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.57
Residue 217: the 'disordered' region

Full DNAAF2 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

DNAAF2 p.Pro217Leu Uncertain significance ★ ⚠ same residue
DNAAF2 p.Pro217= Likely benign ★ same residue
DNAAF2 p.Ala275fs Pathogenic/Likely pathogenic ★★ same condition
DNAAF2 p.Ser506fs Pathogenic ★★ same condition
DNAAF2 p.Ser124_Tyr131del Uncertain significance ★★ same condition
DNAAF2 p.Ala233fs Pathogenic ★ same condition
DNAAF2 p.Ala364fs Pathogenic ★ same condition
DNAAF2 p.Asn632fs 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/dnaaf2-p-pro217fs (accessed [today's date]).

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