Is ODAD1 p.Arg85Pro (c.254G>C) pathogenic?

ODAD1 p.Arg85Pro (c.254G>C) is classified Uncertain significance in ODAD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: ambiguous (0.5489); Very rare (popmax 0.00273%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with ODAD1 p.Arg85Pro (c.254G>C)?

ODAD1 p.Arg85Pro (c.254G>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is ODAD1 p.Arg85Pro (c.254G>C) in the general population?

ODAD1 p.Arg85Pro (c.254G>C) is very rare (popmax 0.00273%, afr) (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 ODAD1 p.Arg85Pro (c.254G>C)?

AlphaMissense predicts ambiguous (score 0.5489) — an in-silico prediction, not a clinical call.

ODAD1 p.Arg85Pro

c.254G>C · VCV3923826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5489 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00273%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.5489	ambiguous · top 9% in ODAD1
REVEL	0.068	moderately benign-leaning
SaProt	LLR -13.18	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -2.9
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.066 · regional, not allelic
Overall
CADD	10.85	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R48P vs ClinVar R85P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00273% African / African-American · 2/73,166 alleles

Filtering AF 0.000454% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00017%

Overall 0.000387% 6/1,551,644 alleles · very rare exomes 6/1,399,372 · genomes 0/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00273%	36,583
European (non-Finnish)	0.000349%	286,747

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: ODAD1
Protein: p.Arg85Pro
Coding: c.254G>C
MANE Select: NM_001364171
Type: single nucleotide variant
Location: chr19:48318493 (GRCh38)
Gene constraint: LOEUF 0.904 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.25 · 1 PDB

Full ODAD1 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

ODAD1 p.Arg85Gln Uncertain significance ★★ ⚠ same residue
ODAD1 p.Arg85Trp Uncertain significance ★ ⚠ same residue
ODAD1 c.1502+5G>A Pathogenic/Likely pathogenic ★★ same condition
ODAD1 c.1503-2A>G Likely pathogenic ★★ same condition
ODAD1 c.597+1G>A Pathogenic/Likely pathogenic ★★ same condition
ODAD1 c.598-2A>G Pathogenic ★★ same condition
ODAD1 p.Ala285Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
ODAD1 p.Arg150Ter 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/odad1-p-arg85pro (accessed [today's date]).

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