Is DNAAF3 p.Leu407= (c.1219T>C) pathogenic?

DNAAF3 p.Leu407= (c.1219T>C) is classified Likely benign in DNAAF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-23). Very rare (popmax 0.00113%, sas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF3 p.Leu407= (c.1219T>C)?

DNAAF3 p.Leu407= (c.1219T>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF3 p.Leu407= (c.1219T>C) in the general population?

DNAAF3 p.Leu407= (c.1219T>C) is very rare (popmax 0.00113%, sas) (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.Leu407=

c.1219T>C · rs1416853193 · VCV1772260

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00113%, sas)

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	GERP -2.4, phastCons 0.99
Overall
CADD	9.094	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00113% South Asian · 1/88,772 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000276% 4/1,449,988 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00113%	88,772
European (non-Finnish)	0.000256%	391,307

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.Leu407=
Coding: c.1219T>C
MANE Select: NM_001256715
dbSNP: rs1416853193
Type: single nucleotide variant
Location: chr19:55159552 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.06

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

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

DNAAF3 p.Leu407Val Uncertain significance ★ same residue
DNAAF3 c.789+1G>C Likely pathogenic ★★ same condition
DNAAF3 p.Asn252Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
DNAAF3 p.Gln301Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF3 c.789+5G>C Uncertain significance ★★ same condition
DNAAF3 c.-37G>A Uncertain significance ★★ same condition
DNAAF3 p.Ala128Thr Uncertain significance ★★ ⚠ same condition
DNAAF3 p.Ala256Gly 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/dnaaf3-p-leu407 (accessed [today's date]).

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