Is DNAI1 p.Cys339Phe (c.1016G>T) pathogenic?

DNAI1 p.Cys339Phe (c.1016G>T) is classified Uncertain significance in DNAI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: likely benign (0.2981); Ultra-rare (popmax 0.0134%, eas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAI1 p.Cys339Phe (c.1016G>T)?

DNAI1 p.Cys339Phe (c.1016G>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAI1 p.Cys339Phe (c.1016G>T) in the general population?

DNAI1 p.Cys339Phe (c.1016G>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

What do computational predictors say about DNAI1 p.Cys339Phe (c.1016G>T)?

AlphaMissense predicts likely benign (score 0.2981) — an in-silico prediction, not a clinical call.

DNAI1 p.Cys339Phe

c.1016G>T · rs777922183 · VCV2548761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2981 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.2981	likely benign
REVEL	0.546	indeterminate
SaProt	LLR -11.70	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -0.79, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 62 kb · p 0.35 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,886 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000434% 7/1,612,960 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,481
European (non-Finnish)	8.48e-05%	1,178,970

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.Cys339Phe
Coding: c.1016G>T
MANE Select: NM_012144
dbSNP: rs777922183
Type: single nucleotide variant
Location: chr9:34500836 (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 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
DNAI1 c.1719-1G>A 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-cys339phe (accessed [today's date]).

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