Is DNAI2 p.Arg347Cys (c.1039C>T) pathogenic?

DNAI2 p.Arg347Cys (c.1039C>T) is classified Uncertain significance in DNAI2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-16). AlphaMissense: likely pathogenic (0.8952); Very rare (popmax 0.00667%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAI2 p.Arg347Cys (c.1039C>T)?

DNAI2 p.Arg347Cys (c.1039C>T) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 9 (ClinVar).

How common is DNAI2 p.Arg347Cys (c.1039C>T) in the general population?

DNAI2 p.Arg347Cys (c.1039C>T) is very rare (popmax 0.00667%, 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 DNAI2 p.Arg347Cys (c.1039C>T)?

AlphaMissense predicts likely pathogenic (score 0.8952) — an in-silico prediction, not a clinical call.

DNAI2 p.Arg347Cys

c.1039C>T · rs774602317 · VCV2449177

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8952 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.8952	likely pathogenic
REVEL	0.474	indeterminate
SaProt	LLR -13.18	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 7.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 32 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	33.0	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 0.00667% Admixed American · 4/60,002 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00198% 32/1,614,102 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,001
European (non-Finnish)	0.0022%	45,387
South Asian	0.0022%	45,540

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: DNAI2
Protein: p.Arg347Cys
Coding: c.1039C>T
MANE Select: NM_023036
dbSNP: rs774602317
Type: single nucleotide variant
Location: chr17:74305270 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.27 · 1 PDB

Full DNAI2 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 9

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

DNAI2 p.Arg347His Uncertain significance ★★ ⚠ same residue
DNAI2 p.Arg347Pro Uncertain significance ★ ⚠ same residue
DNAI2 c.1348-1G>A Likely pathogenic ★★ same condition
DNAI2 c.1494+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNAI2 c.1494+1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAI2 c.1495-2A>T Likely pathogenic ★★ same condition
DNAI2 c.346-3T>G Pathogenic/Likely pathogenic ★★ same condition
DNAI2 c.610+1G>A 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/dnai2-p-arg347cys (accessed [today's date]).

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