Is ODAD2 p.Pro651Ser (c.1951C>T) pathogenic?

ODAD2 p.Pro651Ser (c.1951C>T) is classified Uncertain significance in ODAD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.7366); Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia.

What condition is associated with ODAD2 p.Pro651Ser (c.1951C>T)?

ODAD2 p.Pro651Ser (c.1951C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is ODAD2 p.Pro651Ser (c.1951C>T) in the general population?

ODAD2 p.Pro651Ser (c.1951C>T) 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 ODAD2 p.Pro651Ser (c.1951C>T)?

AlphaMissense predicts likely pathogenic (score 0.7366) — an in-silico prediction, not a clinical call.

ODAD2 p.Pro651Ser

c.1951C>T · VCV4632050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7366 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.7366	likely pathogenic
REVEL	0.728	pathogenic-leaning
SaProt	LLR -10.35	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 132 kb · p 0.67 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: ODAD2
Protein: p.Pro651Ser
Coding: c.1951C>T
MANE Select: NM_018076
Type: single nucleotide variant
Location: chr10:27940598 (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 — 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 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 p.Glu658Ter Pathogenic ★★ same condition
ODAD2 c.1386+5G>A Uncertain significance ★★ same condition
ODAD2 p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
ODAD2 p.Ala128Gly Uncertain significance ★★ ⚠ same condition
ODAD2 p.Ala560Thr Uncertain significance ★★ ⚠ 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-pro651ser (accessed [today's date]).

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