Is DNAI1 p.Lys247= (c.741G>A) pathogenic?

DNAI1 p.Lys247= (c.741G>A) is classified Likely benign in DNAI1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-20). Ultra-rare (popmax 0.048%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAI1 p.Lys247= (c.741G>A)?

DNAI1 p.Lys247= (c.741G>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAI1 p.Lys247= (c.741G>A) in the general population?

DNAI1 p.Lys247= (c.741G>A) is ultra-rare (popmax 0.048%, 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.Lys247=

c.741G>A · rs562408105 · VCV1088722

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.048%, 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 1.8	GERP -4.5, phastCons 1
Overall
CADD	6.808	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.048% African / African-American · 36/75,050 alleles

Filtering AF 0.0356% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00279% 45/1,614,210 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.048%	2,085
Remaining individualsnot grpmax-eligible	0.0064%	15,627
South Asian	0.0011%	91,078
European (non-Finnish)	0.000339%	295,009

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.Lys247=
Coding: c.741G>A
MANE Select: NM_012144
dbSNP: rs562408105
Type: single nucleotide variant
Location: chr9:34493253 (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

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.Lys247Asn Uncertain significance ★ ⚠ same residue
DNAI1 c.1019+5G>C Pathogenic/Likely pathogenic ★★ same condition
DNAI1 c.1063+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNAI1 c.1063+1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAI1 c.1402-1G>A Likely pathogenic ★★ same condition
DNAI1 c.1490-2A>G Likely pathogenic ★★ same condition
DNAI1 c.1569+1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAI1 c.1570-1G>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/dnai1-p-lys247 (accessed [today's date]).

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