Is DNAAF2 p.Ser8Ter (c.23C>A) pathogenic?

DNAAF2 p.Ser8Ter (c.23C>A) is classified Pathogenic in DNAAF2 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2008-12-04). Ultra-rare (popmax 0.0168%, mid); Associated with primary ciliary dyskinesia 10.

What condition is associated with DNAAF2 p.Ser8Ter (c.23C>A)?

DNAAF2 p.Ser8Ter (c.23C>A) is associated with primary ciliary dyskinesia 10, primary ciliary dyskinesia 1 (ClinVar).

How common is DNAAF2 p.Ser8Ter (c.23C>A) in the general population?

DNAAF2 p.Ser8Ter (c.23C>A) is ultra-rare (popmax 0.0168%, mid) (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.Ser8Ter

c.23C>A · rs137853191 · VCV529

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

Conditions

primary ciliary dyskinesia 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.7, phastCons 1
Overall
CADD	37.0	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 0.0168% Middle Eastern · 1/5,964 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000283% 4/1,411,476 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,964
European (non-Finnish)	0.00026%	384,977

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.Ser8Ter
Coding: c.23C>A
MANE Select: NM_018139
dbSNP: rs137853191
Type: single nucleotide variant
Location: chr14:49635127 (GRCh38)
Gene constraint: LOEUF 1.811 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.57

Full DNAAF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia 1

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.Gln504Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF2 p.Glu243Ter Likely pathogenic ★★ same condition
DNAAF2 p.Arg111Pro Uncertain significance ★★ ⚠ same condition
DNAAF2 p.Arg22Gln Uncertain significance ★★ ⚠ same condition
DNAAF2 p.Arg260Leu Uncertain significance ★★ ⚠ same condition
DNAAF2 p.Arg542Trp Uncertain significance ★★ ⚠ same condition
DNAAF2 p.Arg609Gly Uncertain significance ★★ ⚠ same condition
DNAAF2 p.Gln573= Uncertain significance ★★ 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-ser8ter (accessed [today's date]).

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