Is DNAAF5 p.Asp521= (c.1563C>T) pathogenic?

DNAAF5 p.Asp521= (c.1563C>T) is classified Likely benign in DNAAF5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-02). Very rare (popmax 0.0029%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF5 p.Asp521= (c.1563C>T)?

DNAAF5 p.Asp521= (c.1563C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF5 p.Asp521= (c.1563C>T) in the general population?

DNAAF5 p.Asp521= (c.1563C>T) is very rare (popmax 0.0029%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DNAAF5 p.Asp521=

c.1563C>T · rs754692782 · VCV1775315

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0029%, nfe)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.174	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.1
Overall
CADD	0.629	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0029% European (non-Finnish) · 34/1,172,880 alleles

Filtering AF 0.00209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00184%

Overall 0.00238% 38/1,598,436 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0029%	34,496
South Asian	0.00227%	44,140
Admixed American	0.00173%	57,866
Remaining individualsnot grpmax-eligible	0.00162%	61,878

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: DNAAF5
Protein: p.Asp521=
Coding: c.1563C>T
MANE Select: NM_017802
dbSNP: rs754692782
Type: single nucleotide variant
Location: chr7:761845 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.80

Full DNAAF5 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

DNAAF5 c.1470+1G>A Likely pathogenic ★★ same condition
DNAAF5 c.1615-2A>G Likely pathogenic ★★ same condition
DNAAF5 p.Arg253Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF5 p.Cys500Phe Pathogenic/Likely pathogenic ★★ ⚠ same condition
DNAAF5 p.Leu795Pro Pathogenic/Likely pathogenic ★★ same condition
DNAAF5 p.Trp309Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF5 c.780+6T>A Uncertain significance ★★ same condition
DNAAF5 c.905+4C>T 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/dnaaf5-p-asp521 (accessed [today's date]).

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