Is ODAD2 p.Ala757= (c.2271C>G) pathogenic?

ODAD2 p.Ala757= (c.2271C>G) is classified Likely benign in ODAD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-29). Ultra-rare (popmax 0.0253%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with ODAD2 p.Ala757= (c.2271C>G)?

ODAD2 p.Ala757= (c.2271C>G) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 23 (ClinVar).

How common is ODAD2 p.Ala757= (c.2271C>G) in the general population?

ODAD2 p.Ala757= (c.2271C>G) is ultra-rare (popmax 0.0253%, afr) (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.Ala757=

c.2271C>G · rs112483026 · VCV739408

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, afr)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1.9, phastCons 1
Overall
CADD	6.699	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% African / African-American · 19/75,006 alleles

Filtering AF 0.0165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00477% 77/1,613,830 alleles · ultra-rare exomes 75/1,461,574 · genomes 2/152,256 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.04%	2,500
African / African-Americangrpmax	0.0253%	3,948
Admixed American	0.0233%	4,284
European (non-Finnish)	0.00153%	65,545
South Asian	0.0011%	91,064

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala757=
Coding: c.2271C>G
MANE Select: NM_018076
dbSNP: rs112483026
Type: single nucleotide variant
Location: chr10:27935234 (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

Also linked: primary ciliary dyskinesia 23

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.Ala757Asp 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
ODAD2 p.Gln657Ter 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-ala757 (accessed [today's date]).

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