Is ODAD2 p.Arg970Ser (c.2908C>A) pathogenic?

ODAD2 p.Arg970Ser (c.2908C>A) is classified Uncertain significance in ODAD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-19). AlphaMissense: likely benign (0.233); Ultra-rare (popmax 0.0233%, amr); Associated with primary ciliary dyskinesia 23.

What condition is associated with ODAD2 p.Arg970Ser (c.2908C>A)?

ODAD2 p.Arg970Ser (c.2908C>A) is associated with primary ciliary dyskinesia 23, primary ciliary dyskinesia (ClinVar).

How common is ODAD2 p.Arg970Ser (c.2908C>A) in the general population?

ODAD2 p.Arg970Ser (c.2908C>A) is ultra-rare (popmax 0.0233%, amr) (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 ODAD2 p.Arg970Ser (c.2908C>A)?

AlphaMissense predicts likely benign (score 0.233) — an in-silico prediction, not a clinical call.

ODAD2 p.Arg970Ser

c.2908C>A · rs776293552 · VCV1681342

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.233 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary ciliary dyskinesia 23

Computational evidence

Protein change
AlphaMissense	0.233	likely benign
REVEL	0.567	indeterminate
SaProt	LLR -5.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.9, phastCons 0.059
Regional constraint	o/e 0.98	unconstrained · MANE · 132 kb · p 0.67 · regional, not allelic
Overall
CADD	19.21	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0233% Admixed American · 14/59,986 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00136% 22/1,613,978 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,285
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000593%	168,573

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.Arg970Ser
Coding: c.2908C>A
MANE Select: NM_018076
dbSNP: rs776293552
Type: single nucleotide variant
Location: chr10:27860738 (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

Also linked: primary ciliary dyskinesia

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.Arg970His Uncertain significance ★★ ⚠ same residue
ODAD2 p.Arg970Cys Uncertain significance ★ ⚠ same residue
ODAD2 c.2097+1G>A Pathogenic/Likely pathogenic ★★ same condition
ODAD2 c.2097+1G>T Pathogenic/Likely pathogenic ★★ same condition
ODAD2 c.2495+1G>A Pathogenic ★★ same condition
ODAD2 c.2800-2A>G Pathogenic/Likely pathogenic ★★ same condition
ODAD2 c.383-1G>T Likely pathogenic ★★ same condition
ODAD2 c.576-2A>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/odad2-p-arg970ser (accessed [today's date]).

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