Is DNAI2 p.Ser398= (c.1194G>A) pathogenic?

DNAI2 p.Ser398= (c.1194G>A) is classified Conflicting classifications of pathogenicity in DNAI2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-01). Rare (popmax 0.124%, sas); Associated with primary ciliary dyskinesia 9.

What condition is associated with DNAI2 p.Ser398= (c.1194G>A)?

DNAI2 p.Ser398= (c.1194G>A) is associated with primary ciliary dyskinesia 9, primary ciliary dyskinesia (ClinVar).

How common is DNAI2 p.Ser398= (c.1194G>A) in the general population?

DNAI2 p.Ser398= (c.1194G>A) is rare (popmax 0.124%, sas) (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.Ser398=

c.1194G>A · rs556547267 · VCV703212

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.124%, sas)

Conditions

primary ciliary dyskinesia 9

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 -11	GERP -2.4
Overall
CADD	1.045	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.124% South Asian · 113/91,068 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0985%

Overall 0.00917% 148/1,614,076 alleles · rare exomes 139/1,461,844 · genomes 9/152,232 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.124%	806
Remaining individualsnot grpmax-eligible	0.0048%	20,836
East Asian	0.00446%	22,426
African / African-American	0.004%	25,011
European (non-Finnish)	0.0022%	45,385
Admixed American	0.00167%	60,002

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.Ser398=
Coding: c.1194G>A
MANE Select: NM_023036
dbSNP: rs556547267
Type: single nucleotide variant
Location: chr17:74305425 (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 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

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.Ser398Leu 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-ser398 (accessed [today's date]).

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