Is DNAI2 p.Thr477= (c.1431C>G) pathogenic?

DNAI2 p.Thr477= (c.1431C>G) is classified Benign/Likely benign in DNAI2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-26). Low-frequency (popmax 1.81%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAI2 p.Thr477= (c.1431C>G)?

DNAI2 p.Thr477= (c.1431C>G) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 9 (ClinVar).

How common is DNAI2 p.Thr477= (c.1431C>G) in the general population?

DNAI2 p.Thr477= (c.1431C>G) is low-frequency (popmax 1.81%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DNAI2 p.Thr477=

c.1431C>G · rs144035254 · VCV241449

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.81%, afr)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.5	GERP -2.9
Overall
CADD	1.119	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.81% African / African-American · 1,358/75,036 alleles

Filtering AF 1.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.7%

Overall 0.0977% 1,577/1,613,878 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.81%	55
Admixed American	0.162%	619
Remaining individualsnot grpmax-eligible	0.131%	762
Middle Eastern	0.115%	866
South Asian	0.00988%	10,120
European (non-Finnish)	0.00203%	49,168

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.Thr477=
Coding: c.1431C>G
MANE Select: NM_023036
dbSNP: rs144035254
Type: single nucleotide variant
Location: chr17:74310100 (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.Thr477fs Pathogenic ★ 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-thr477 (accessed [today's date]).

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