Is DNAAF5 p.Leu81= (c.243G>A) pathogenic?

DNAAF5 p.Leu81= (c.243G>A) is classified Likely benign in DNAAF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). Very rare (popmax 0.000194%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF5 p.Leu81= (c.243G>A)?

DNAAF5 p.Leu81= (c.243G>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF5 p.Leu81= (c.243G>A) in the general population?

DNAAF5 p.Leu81= (c.243G>A) is very rare (popmax 0.000194%, 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.Leu81=

c.243G>A · VCV3681440

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000194%, nfe)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -1.8, phastCons 1
Overall
CADD	9.274	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000194% European (non-Finnish) · 2/1,031,412 alleles

Filtering AF 3.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000151% 2/1,321,784 alleles · very rare

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.Leu81=
Coding: c.243G>A
MANE Select: NM_017802
Type: single nucleotide variant
Location: chr7:726963 (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.Leu81Met 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
DNAAF5 c.780+6T>A 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-leu81 (accessed [today's date]).

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