Is ODAD2 p.Asp993fs (c.2976del) pathogenic?

ODAD2 p.Asp993fs (c.2976del) is classified Uncertain significance in ODAD2 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 0.00144%, nfe); Associated with primary ciliary dyskinesia 23.

What condition is associated with ODAD2 p.Asp993fs (c.2976del)?

ODAD2 p.Asp993fs (c.2976del) is associated with primary ciliary dyskinesia 23 (ClinVar).

How common is ODAD2 p.Asp993fs (c.2976del) in the general population?

ODAD2 p.Asp993fs (c.2976del) is very rare (popmax 0.00144%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

ODAD2 p.Asp993fs

c.2976del · rs1327805728 · VCV561182

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Conditions

primary ciliary dyskinesia 23

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (19 of 20, 45 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% European (non-Finnish) · 17/1,180,036 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00105% 17/1,614,012 alleles · very rare exomes 10/1,461,850 · genomes 7/152,162 · joint denominator

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: ODAD2
Protein: p.Asp993fs
Coding: c.2976del
MANE Select: NM_018076
dbSNP: rs1327805728
Type: Deletion
Location: chr10:27860670 (GRCh38)
Gene constraint: LOEUF 0.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 1 PDB

Full ODAD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 23 — 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

ODAD2 p.Asp993= Benign/Likely benign ★★ same residue
ODAD2 p.Leu802_Val803insTer Pathogenic ★★ same condition
ODAD2 p.Tyr698fs Pathogenic/Likely pathogenic ★★ same condition
ODAD2 c.383-6del Benign/Likely benign ★★ same condition
ODAD2 c.1387-808_1744-1080del Likely pathogenic ★ same condition
ODAD2 c.382+995_936+335del Pathogenic ★ same condition
ODAD2 p.Asn914_Leu915insTer Pathogenic ★ same condition
ODAD2 p.Asn914fs 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/odad2-p-asp993fs (accessed [today's date]).

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