Is DNAAF5 p.Trp73Ser (c.218G>C) pathogenic?

DNAAF5 p.Trp73Ser (c.218G>C) is classified Uncertain significance in DNAAF5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-01-06). AlphaMissense: likely pathogenic (0.9273); Very rare (popmax 0.00323%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF5 p.Trp73Ser (c.218G>C)?

DNAAF5 p.Trp73Ser (c.218G>C) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 18 (ClinVar).

How common is DNAAF5 p.Trp73Ser (c.218G>C) in the general population?

DNAAF5 p.Trp73Ser (c.218G>C) is very rare (popmax 0.00323%, amr) (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.Trp73Ser (c.218G>C)?

AlphaMissense predicts likely pathogenic (score 0.9273) — an in-silico prediction, not a clinical call.

DNAAF5 p.Trp73Ser

c.218G>C · rs915848808 · VCV1787401

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9273 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00323%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.9273	likely pathogenic · top 5% in DNAAF5
REVEL	0.184	benign-leaning
SaProt	LLR -8.39	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 0.91, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 59 kb · p 0.0084 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00323% Admixed American · 1/31,006 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00147%

Overall 0.00209% 28/1,340,958 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00323%	31,006
European (non-Finnish)	0.00249%	40,114
Remaining individualsnot grpmax-eligible	0.00203%	49,142

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.Trp73Ser
Coding: c.218G>C
MANE Select: NM_017802
dbSNP: rs915848808
Type: single nucleotide variant
Location: chr7:726938 (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

Also linked: primary ciliary dyskinesia 18

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.Trp73Ter Pathogenic ★ 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-trp73ser (accessed [today's date]).

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