Is DNAAF5 p.Pro619= (c.1857G>A) pathogenic?

DNAAF5 p.Pro619= (c.1857G>A) is classified Likely benign in DNAAF5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-03). Ultra-rare (popmax 0.015%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF5 p.Pro619= (c.1857G>A)?

DNAAF5 p.Pro619= (c.1857G>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF5 p.Pro619= (c.1857G>A) in the general population?

DNAAF5 p.Pro619= (c.1857G>A) is ultra-rare (popmax 0.015%, amr) (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.Pro619=

c.1857G>A · rs764779473 · VCV1781430

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.009	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.8	GERP -2.6
Overall
CADD	0.379	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/60,030 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.00171% 25/1,461,620 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,670
South Asian	0.0022%	45,542
Remaining individualsnot grpmax-eligible	0.0016%	62,506
African / African-American	0.00133%	75,044
European (non-Finnish)	0.00102%	98,333

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.Pro619=
Coding: c.1857G>A
MANE Select: NM_017802
dbSNP: rs764779473
Type: single nucleotide variant
Location: chr7:770544 (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.Pro619Leu Uncertain significance ★★ ⚠ same residue
DNAAF5 p.Pro619Arg 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-pro619 (accessed [today's date]).

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