Is DNAAF5 p.Ile563= (c.1689T>C) pathogenic?

DNAAF5 p.Ile563= (c.1689T>C) is classified Benign/Likely benign in DNAAF5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Rare (popmax 0.991%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF5 p.Ile563= (c.1689T>C)?

DNAAF5 p.Ile563= (c.1689T>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF5 p.Ile563= (c.1689T>C) in the general population?

DNAAF5 p.Ile563= (c.1689T>C) is rare (popmax 0.991%, afr) (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.Ile563=

c.1689T>C · rs151227818 · VCV241198

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.991%, afr)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.051	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -3.4, phastCons 0.001
Overall
CADD	1.407	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.991% African / African-American · 744/75,066 alleles

Filtering AF 0.932% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.909%

Overall 0.0519% 838/1,613,290 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.991%	101
Remaining individualsnot grpmax-eligible	0.0784%	1,275
Admixed American	0.0666%	1,501
Middle Eastern	0.033%	3,031
South Asian	0.0011%	91,086
European (non-Finnish)	0.000169%	590,019

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.Ile563=
Coding: c.1689T>C
MANE Select: NM_017802
dbSNP: rs151227818
Type: single nucleotide variant
Location: chr7:763880 (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 p.Ile563Val Likely benign ★★ same residue
DNAAF5 p.Ile563Met Uncertain significance ★ ⚠ same residue
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

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-ile563 (accessed [today's date]).

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