Is DNAI2 p.Ala283= (c.849T>C) pathogenic?

DNAI2 p.Ala283= (c.849T>C) is classified Likely benign in DNAI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). Ultra-rare (popmax 0.022%, sas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAI2 p.Ala283= (c.849T>C)?

DNAI2 p.Ala283= (c.849T>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAI2 p.Ala283= (c.849T>C) in the general population?

DNAI2 p.Ala283= (c.849T>C) is ultra-rare (popmax 0.022%, 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.Ala283=

c.849T>C · rs531514142 · VCV1078241

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, sas)

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 -7.7	GERP -3.6
Overall
CADD	0.247	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.022% South Asian · 20/91,080 alleles

Filtering AF 0.0145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00149% 24/1,613,330 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.022%	4,554
African / African-American	0.00267%	37,458
East Asian	0.00223%	44,838
Remaining individualsnot grpmax-eligible	0.0016%	62,500

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.Ala283=
Coding: c.849T>C
MANE Select: NM_023036
dbSNP: rs531514142
Type: single nucleotide variant
Location: chr17:74299842 (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

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-ala283 (accessed [today's date]).

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