Is DNAAF3 p.Pro352= (c.1056G>A) pathogenic?

DNAAF3 p.Pro352= (c.1056G>A) is classified Benign/Likely benign in DNAAF3 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 60.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF3 p.Pro352= (c.1056G>A)?

DNAAF3 p.Pro352= (c.1056G>A) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 2 (ClinVar).

How is Primary ciliary dyskinesia inherited?

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

DNAAF3 p.Pro352=

Q: How common is DNAAF3 p.Pro352= (c.1056G>A) in the general population?

DNAAF3 p.Pro352= (c.1056G>A) is common (popmax 60.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1056G>A · rs891187 · VCV257680

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 60.6%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.132	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -2
Overall
CADD	0.931	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 60.6% African / African-American · 43,291/71,442 alleles

Filtering AF 60.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 59.9%

Overall 24.1% 314,598/1,302,950 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	60.6%	2
Middle Eastern	32%	3
South Asian	29.1%	3
Remaining individualsnot grpmax-eligible	27.2%	4
Finnishnot grpmax-eligible	24%	4
East Asian	23.7%	4
Ashkenazi Jewishnot grpmax-eligible	21.5%	5
European (non-Finnish)	21.3%	5
Admixed American	15.7%	6
Amishnot grpmax-eligible	14.9%	7

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.Pro352=
Coding: c.1056G>A
MANE Select: NM_001256715
dbSNP: rs891187
Type: single nucleotide variant
Location: chr19:55160006 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.06
Residue 352: the 'disordered' region

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

Also linked: primary ciliary dyskinesia 2

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.Pro352Leu Uncertain significance ★ ⚠ same residue
DNAAF3 c.789+1G>C Likely pathogenic ★★ same condition
DNAAF3 p.Asn252Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
DNAAF3 p.Gln301Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF3 c.789+5G>C Uncertain significance ★★ same condition
DNAAF3 c.-37G>A Uncertain significance ★★ same condition
DNAAF3 p.Ala128Thr Uncertain significance ★★ ⚠ same condition
DNAAF3 p.Ala256Gly 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/dnaaf3-p-pro352 (accessed [today's date]).

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