Is ODAD1 p.Phe166Ser (c.497T>C) pathogenic?

ODAD1 p.Phe166Ser (c.497T>C) is classified Uncertain significance in ODAD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-06). AlphaMissense: likely pathogenic (0.9196); Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia.

What condition is associated with ODAD1 p.Phe166Ser (c.497T>C)?

ODAD1 p.Phe166Ser (c.497T>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is ODAD1 p.Phe166Ser (c.497T>C) in the general population?

ODAD1 p.Phe166Ser (c.497T>C) is absent from gnomAD v4.1 (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.Phe166Ser (c.497T>C)?

AlphaMissense predicts likely pathogenic (score 0.9196) — an in-silico prediction, not a clinical call.

ODAD1 p.Phe166Ser

c.497T>C · rs2515949291 · VCV2198844

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9196 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.9196	likely pathogenic · top 1% in ODAD1
REVEL	0.819	moderately pathogenic-leaning
SaProt	LLR -9.88	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.066 · regional, not allelic
Overall
CADD	25.6	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 F129S vs ClinVar F166S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ODAD1
Protein: p.Phe166Ser
Coding: c.497T>C
MANE Select: NM_001364171
dbSNP: rs2515949291
Type: single nucleotide variant
Location: chr19:48311653 (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.Phe166_Asp167insArg 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
ODAD1 p.Gln120Ter 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-phe166ser (accessed [today's date]).

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