Is DNAI2 p.Arg506= (c.1516C>A) pathogenic?

DNAI2 p.Arg506= (c.1516C>A) is classified Likely benign in DNAI2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-11). Ultra-rare (popmax 0.0734%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with DNAI2 p.Arg506= (c.1516C>A)?

DNAI2 p.Arg506= (c.1516C>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAI2 p.Arg506= (c.1516C>A) in the general population?

DNAI2 p.Arg506= (c.1516C>A) is ultra-rare (popmax 0.0734%, nfe) (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.Arg506=

c.1516C>A · rs141581673 · VCV525548

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0734%, nfe)

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 0.54	GERP 1.2, phastCons 0.98
Overall
CADD	5.047	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0734% European (non-Finnish) · 866/1,179,726 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0677%

Overall 0.0585% 943/1,611,708 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0734%	1,362
Admixed American	0.0717%	1,396
Remaining individualsnot grpmax-eligible	0.0305%	3,279
African / African-American	0.0107%	9,370
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
Finnishnot grpmax-eligible	0.00627%	15,940
South Asian	0.0011%	90,982

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.Arg506=
Coding: c.1516C>A
MANE Select: NM_023036
dbSNP: rs141581673
Type: single nucleotide variant
Location: chr17:74312024 (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 p.Arg506Ter Pathogenic/Likely pathogenic ★★ same residue
DNAI2 p.Arg506Gln Uncertain significance ★ same residue
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

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-arg506 (accessed [today's date]).

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