Is DNAAF5 p.Arg350Trp (c.1048C>T) pathogenic?

DNAAF5 p.Arg350Trp (c.1048C>T) is classified Uncertain significance in DNAAF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-04). AlphaMissense: likely pathogenic (0.8601); Ultra-rare (popmax 0.0242%, sas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF5 p.Arg350Trp (c.1048C>T)?

DNAAF5 p.Arg350Trp (c.1048C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF5 p.Arg350Trp (c.1048C>T) in the general population?

DNAAF5 p.Arg350Trp (c.1048C>T) is ultra-rare (popmax 0.0242%, sas) (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.Arg350Trp (c.1048C>T)?

AlphaMissense predicts likely pathogenic (score 0.8601) — an in-silico prediction, not a clinical call.

DNAAF5 p.Arg350Trp

c.1048C>T · rs377089514 · VCV1776030

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8601 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.8601	likely pathogenic · top 10% in DNAAF5
REVEL	0.757	pathogenic-leaning
SaProt	LLR -15.72	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.76, phastCons 0.99
Regional constraint	o/e 1.08	unconstrained · MANE · 59 kb · p 0.0084 · regional, not allelic
Overall
CADD	26.1	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

Grpmax group 0.0242% South Asian · 22/91,082 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.0031% 50/1,614,064 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0242%	4,140
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0064%	15,626
Admixed American	0.00333%	30,004
East Asian	0.00223%	44,886
European (non-Finnish)	0.00169%	58,998

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.Arg350Trp
Coding: c.1048C>T
MANE Select: NM_017802
dbSNP: rs377089514
Type: single nucleotide variant
Location: chr7:754612 (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.Arg350= Likely benign ★★ same residue
DNAAF5 p.Arg350Gln 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

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-arg350trp (accessed [today's date]).

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