Is DNAAF5 p.Arg343His (c.1028G>A) pathogenic?

DNAAF5 p.Arg343His (c.1028G>A) is classified Likely benign in DNAAF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-19). AlphaMissense: likely benign (0.0612); Very rare (popmax 0.00446%, eas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF5 p.Arg343His (c.1028G>A)?

DNAAF5 p.Arg343His (c.1028G>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF5 p.Arg343His (c.1028G>A) in the general population?

DNAAF5 p.Arg343His (c.1028G>A) is very rare (popmax 0.00446%, eas) (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.Arg343His (c.1028G>A)?

AlphaMissense predicts likely benign (score 0.0612) — an in-silico prediction, not a clinical call.

DNAAF5 p.Arg343His

c.1028G>A · VCV3272530

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0612 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.0612	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -9.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -3.7
Regional constraint	o/e 1.08	unconstrained · MANE · 59 kb · p 0.0084 · regional, not allelic
Overall
CADD	3.548	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 0.00446% East Asian · 2/44,846 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.0013% 19/1,460,356 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,423
Remaining individualsnot grpmax-eligible	0.0032%	31,219
European (non-Finnish)	0.00119%	84,218
South Asian	0.0011%	90,946

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.Arg343His
Coding: c.1028G>A
MANE Select: NM_017802
Type: single nucleotide variant
Location: chr7:754592 (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.Arg343Cys Conflicting classifications of pathogenicity ★ ⚠ 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-arg343his (accessed [today's date]).

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