Is DNAAF2 p.Ala563Ser (c.1687G>T) pathogenic?

DNAAF2 p.Ala563Ser (c.1687G>T) is classified Conflicting classifications of pathogenicity in DNAAF2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-15). AlphaMissense: likely benign (0.0743); Rare (popmax 0.33%, eas); Associated with primary ciliary dyskinesia 10.

What condition is associated with DNAAF2 p.Ala563Ser (c.1687G>T)?

DNAAF2 p.Ala563Ser (c.1687G>T) is associated with primary ciliary dyskinesia 10, primary ciliary dyskinesia (ClinVar).

How common is DNAAF2 p.Ala563Ser (c.1687G>T) in the general population?

DNAAF2 p.Ala563Ser (c.1687G>T) is rare (popmax 0.33%, eas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

What do computational predictors say about DNAAF2 p.Ala563Ser (c.1687G>T)?

AlphaMissense predicts likely benign (score 0.0743) — an in-silico prediction, not a clinical call.

DNAAF2 p.Ala563Ser

c.1687G>T · rs138511448 · VCV313277

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0743 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.33%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 10

Computational evidence

Protein change
AlphaMissense	0.0743	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -5.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -3.3, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 9,604 bp · p 0.00019 · regional, not allelic
Overall
CADD	12.78	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.33% East Asian · 148/44,882 alleles

Filtering AF 0.286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.27%

Overall 0.0119% 192/1,614,036 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.33%	303
South Asian	0.0351%	2,846
Remaining individualsnot grpmax-eligible	0.016%	6,249
Admixed American	0.00167%	60,028
European (non-Finnish)	8.48e-05%	1,179,903

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.Ala563Ser
Coding: c.1687G>T
MANE Select: NM_018139
dbSNP: rs138511448
Type: single nucleotide variant
Location: chr14:49633463 (GRCh38)
Gene constraint: LOEUF 1.811 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.57

Full DNAAF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

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.Ala563= 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-ala563ser (accessed [today's date]).

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