Is DNAI1 p.Ala501= (c.1503C>T) pathogenic?

DNAI1 p.Ala501= (c.1503C>T) is classified Likely benign in DNAI1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-01-23). Ultra-rare (popmax 0.029%, eas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAI1 p.Ala501= (c.1503C>T)?

DNAI1 p.Ala501= (c.1503C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAI1 p.Ala501= (c.1503C>T) in the general population?

DNAI1 p.Ala501= (c.1503C>T) is ultra-rare (popmax 0.029%, eas) (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.Ala501=

c.1503C>T · rs377601344 · VCV698304

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.473	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.83	GERP -1.7, phastCons 1
Overall
CADD	10.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.029% East Asian · 13/44,888 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00465% 75/1,613,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0752%	1,329
East Asiangrpmax	0.029%	3,453
Admixed American	0.005%	20,003
European (non-Finnish)	0.00102%	98,332

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala501=
Coding: c.1503C>T
MANE Select: NM_012144
dbSNP: rs377601344
Type: single nucleotide variant
Location: chr9:34513125 (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.Ala501fs Pathogenic/Likely pathogenic ★★ 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-ala501 (accessed [today's date]).

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