Is DNAAF2 p.His443= (c.1329C>T) pathogenic?

DNAAF2 p.His443= (c.1329C>T) is classified Likely benign in DNAAF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0804%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF2 p.His443= (c.1329C>T)?

DNAAF2 p.His443= (c.1329C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF2 p.His443= (c.1329C>T) in the general population?

DNAAF2 p.His443= (c.1329C>T) is ultra-rare (popmax 0.0804%, 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.His443=

c.1329C>T · rs190354993 · VCV416620

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0804%, 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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -1.5
Overall
CADD	3.651	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0804% African / African-American · 60/74,612 alleles

Filtering AF 0.0641% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0582%

Overall 0.0116% 183/1,583,418 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0804%	1,244
Remaining individualsnot grpmax-eligible	0.0178%	5,616
European (non-Finnish)	0.00938%	10,659
Admixed American	0.00174%	57,592
South Asian	0.00112%	88,910

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.His443=
Coding: c.1329C>T
MANE Select: NM_018139
dbSNP: rs190354993
Type: single nucleotide variant
Location: chr14:49633821 (GRCh38)
Gene constraint: LOEUF 1.811 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.57
Residue 443: 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.His443Gln Likely benign ★★ same residue
DNAAF2 p.Gln504Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF2 p.Gln529Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF2 p.Glu130Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF2 p.Glu243Ter Likely pathogenic ★★ same condition
DNAAF2 p.Ala100Gly Uncertain significance ★★ ⚠ same condition
DNAAF2 p.Ala126Val Uncertain significance ★★ ⚠ same condition
DNAAF2 p.Ala211Thr 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-his443 (accessed [today's date]).

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