Is DNAAF2 p.Pro423= (c.1269G>C) pathogenic?

DNAAF2 p.Pro423= (c.1269G>C) is classified Likely benign in DNAAF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-30). Ultra-rare (popmax 0.0574%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF2 p.Pro423= (c.1269G>C)?

DNAAF2 p.Pro423= (c.1269G>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF2 p.Pro423= (c.1269G>C) in the general population?

DNAAF2 p.Pro423= (c.1269G>C) is ultra-rare (popmax 0.0574%, afr) (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.Pro423=

c.1269G>C · rs886038644 · VCV261009

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0574%, afr)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.13	GERP 0.71
Overall
CADD	5.201	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0574% African / African-American · 42/73,154 alleles

Filtering AF 0.0436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0388%

Overall 0.00286% 44/1,536,742 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0574%	1,742
Admixed American	0.00196%	51,134
Remaining individualsnot grpmax-eligible	0.00167%	60,004

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.Pro423=
Coding: c.1269G>C
dbSNP: rs886038644
Type: single nucleotide variant
Location: chr14:49633881 (GRCh38)

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)

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-pro423 (accessed [today's date]).

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