Is DNAI2 p.Asp84fs (c.250del) pathogenic?

DNAI2 p.Asp84fs (c.250del) is classified Pathogenic/Likely pathogenic in DNAI2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-08). Ultra-rare (popmax 0.0187%, afr); Associated with primary ciliary dyskinesia 9.

What condition is associated with DNAI2 p.Asp84fs (c.250del)?

DNAI2 p.Asp84fs (c.250del) is associated with primary ciliary dyskinesia 9, primary ciliary dyskinesia (ClinVar).

How common is DNAI2 p.Asp84fs (c.250del) in the general population?

DNAI2 p.Asp84fs (c.250del) is ultra-rare (popmax 0.0187%, 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.Asp84fs

c.250del · rs769251936 · VCV1071724

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Conditions

primary ciliary dyskinesia 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.1	GERP 1.7, phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,950 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.000929% 15/1,614,130 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,354
Admixed American	0.00167%	60,008

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.Asp84fs
Coding: c.250del
MANE Select: NM_023036
dbSNP: rs769251936
Type: Deletion
Location: chr17:74285105 (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.Asp84= Likely benign ★★ same residue
DNAI2 p.Asn45fs Pathogenic/Likely pathogenic ★★ same condition
DNAI2 p.Phe375fs Pathogenic/Likely pathogenic ★★ same condition
DNAI2 p.Thr475fs Pathogenic/Likely pathogenic ★★ same condition
DNAI2 c.1211+2_1211+5del Likely pathogenic ★ same condition
DNAI2 c.1212-17_1250del Likely pathogenic ★ same condition
DNAI2 c.610+1del Likely pathogenic ★ same condition
DNAI2 p.Ala109fs 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-asp84fs (accessed [today's date]).

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