Is DNAI2 p.Arg189Trp (c.565C>T) pathogenic?

DNAI2 p.Arg189Trp (c.565C>T) is classified Uncertain significance in DNAI2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-11-02). AlphaMissense: likely benign (0.2001); Very rare (popmax 0.00669%, eas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAI2 p.Arg189Trp (c.565C>T)?

DNAI2 p.Arg189Trp (c.565C>T) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 9 (ClinVar).

How common is DNAI2 p.Arg189Trp (c.565C>T) in the general population?

DNAI2 p.Arg189Trp (c.565C>T) is very rare (popmax 0.00669%, 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 DNAI2 p.Arg189Trp (c.565C>T)?

AlphaMissense predicts likely benign (score 0.2001) — an in-silico prediction, not a clinical call.

DNAI2 p.Arg189Trp

c.565C>T · rs138885031 · VCV325010

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2001 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.2001	likely benign
REVEL	0.692	pathogenic-leaning
SaProt	LLR -13.16	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.48, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 32 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	27.9	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 0.00669% East Asian · 3/44,862 alleles

Filtering AF 0.00453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00417%

Overall 0.00489% 79/1,613,898 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,954
European (non-Finnish)	0.00568%	17,612
Remaining individualsnot grpmax-eligible	0.0048%	20,829
South Asian	0.00329%	30,355
African / African-American	0.00267%	37,442
Admixed American	0.00167%	59,966

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.Arg189Trp
Coding: c.565C>T
MANE Select: NM_023036
dbSNP: rs138885031
Type: single nucleotide variant
Location: chr17:74289691 (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.Arg189Gln 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
DNAI2 c.610+1G>T 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-arg189trp (accessed [today's date]).

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