Is DNAAF3 p.Val416= (c.1248G>A) pathogenic?

DNAAF3 p.Val416= (c.1248G>A) is classified Conflicting classifications of pathogenicity in DNAAF3 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-26). Low-frequency (popmax 1.4%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF3 p.Val416= (c.1248G>A)?

DNAAF3 p.Val416= (c.1248G>A) is associated with primary ciliary dyskinesia, cardiomyopathy, familial restrictive, 1, dilated cardiomyopathy 2A (ClinVar).

How common is DNAAF3 p.Val416= (c.1248G>A) in the general population?

DNAAF3 p.Val416= (c.1248G>A) is low-frequency (popmax 1.4%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DNAAF3 p.Val416=

c.1248G>A · rs111250144 · VCV257685

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.4%, 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 looked up on this page · why
Constraint at this position
Conservation	phyloP 0.12	GERP -2.4, phastCons 0.95
Overall
CADD	12.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.4% African / African-American · 1,048/75,040 alleles

Filtering AF 1.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.3%

Overall 0.0724% 1,168/1,613,806 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.4%	72
Remaining individualsnot grpmax-eligible	0.0688%	1,453
Admixed American	0.05%	2,001
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.00364%	27,436
South Asian	0.0022%	45,534

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.Val416=
Coding: c.1248G>A
dbSNP: rs111250144
Type: single nucleotide variant
Location: chr19:55159440 (GRCh38)

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: cardiomyopathy, familial restrictive, 1 dilated cardiomyopathy 2A hypertrophic cardiomyopathy 7

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

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-val416 (accessed [today's date]).

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