Is DNAAF5 p.Glu136Gln (c.406G>C) pathogenic?

DNAAF5 p.Glu136Gln (c.406G>C) is classified Uncertain significance in DNAAF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-28). AlphaMissense: likely pathogenic (0.734); Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF5 p.Glu136Gln (c.406G>C)?

DNAAF5 p.Glu136Gln (c.406G>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF5 p.Glu136Gln (c.406G>C) in the general population?

DNAAF5 p.Glu136Gln (c.406G>C) is absent from gnomAD v4.1 (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 DNAAF5 p.Glu136Gln (c.406G>C)?

AlphaMissense predicts likely pathogenic (score 0.734) — an in-silico prediction, not a clinical call.

DNAAF5 p.Glu136Gln

c.406G>C · rs1781345604 · VCV3227046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.734 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,170,734)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.734	likely pathogenic
REVEL	0.483	indeterminate
SaProt	LLR -12.65	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 1.1, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 59 kb · p 0.0084 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,170,734). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DNAAF5
Protein: p.Glu136Gln
Coding: c.406G>C
MANE Select: NM_017802
dbSNP: rs1781345604
Type: single nucleotide variant
Location: chr7:727126 (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 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
DNAAF5 c.905+4C>T 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-glu136gln (accessed [today's date]).

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