Is DNAI2 p.Ala253= (c.759G>A) pathogenic?

DNAI2 p.Ala253= (c.759G>A) is classified Conflicting classifications of pathogenicity in DNAI2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-05-01). Low-frequency (popmax 1.21%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAI2 p.Ala253= (c.759G>A)?

DNAI2 p.Ala253= (c.759G>A) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 9 (ClinVar).

How common is DNAI2 p.Ala253= (c.759G>A) in the general population?

DNAI2 p.Ala253= (c.759G>A) is low-frequency (popmax 1.21%, 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.Ala253=

c.759G>A · rs142656395 · VCV241453

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.21%, 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 -16	GERP -3.6
Overall
CADD	0.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.21% African / African-American · 906/74,968 alleles

Filtering AF 1.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.12%

Overall 0.0787% 1,269/1,613,374 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.21%	83
Ashkenazi Jewishnot grpmax-eligible	0.311%	322
Middle Eastern	0.231%	433
Remaining individualsnot grpmax-eligible	0.142%	702
Admixed American	0.117%	857
East Asian	0.0178%	5,609
European (non-Finnish)	0.00746%	13,409
South Asian	0.0022%	45,531

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.Ala253=
Coding: c.759G>A
MANE Select: NM_023036
dbSNP: rs142656395
Type: single nucleotide variant
Location: chr17:74299752 (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 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
DNAI2 c.725-2A>C 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-ala253 (accessed [today's date]).

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