Is DNAI1 p.Phe422del (c.1265_1267del) pathogenic?

DNAI1 p.Phe422del (c.12651267del) is classified Conflicting classifications of pathogenicity in DNAI1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-27). Rare (popmax 0.79%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAI1 p.Phe422del (c.1265_1267del)?

DNAI1 p.Phe422del (c.1265_1267del) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 1 (ClinVar).

How common is DNAI1 p.Phe422del (c.1265_1267del) in the general population?

DNAI1 p.Phe422del (c.1265_1267del) is rare (popmax 0.79%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DNAI1 p.Phe422del

c.1265_1267del · rs567346433 · VCV454827

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.79%, 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 · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP -2.2, phastCons 0.95
Overall
CADD	17.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.79% African / African-American · 593/75,044 alleles

Filtering AF 0.738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.717%

Overall 0.0436% 703/1,614,180 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.79%	127
Admixed American	0.108%	924
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0608%	1,645
European (non-Finnish)	0.000254%	393,349

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: DNAI1
Protein: p.Phe422del
Coding: c.1265_1267del
MANE Select: NM_012144
dbSNP: rs567346433
Type: Deletion
Location: chr9:34506826 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.54 · 1 PDB

Full DNAI1 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 1

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

DNAI1 p.Phe422Leu Uncertain significance ★ ⚠ same residue
DNAI1 p.Phe422Ser Uncertain significance ★ ⚠ same residue
DNAI1 p.Ala47fs Pathogenic/Likely pathogenic ★★ same condition
DNAI1 p.Asn450fs Pathogenic/Likely pathogenic ★★ same condition
DNAI1 p.Asp114fs Pathogenic/Likely pathogenic ★★ same condition
DNAI1 p.Asp509_Tyr510insTer Pathogenic/Likely pathogenic ★★ same condition
DNAI1 p.Leu188_Thr189insTer Pathogenic ★★ same condition
DNAI1 p.Pro488fs 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/dnai1-p-phe422del (accessed [today's date]).

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