Is ODAD3 p.Pro50Ser (c.148C>T) pathogenic?

ODAD3 p.Pro50Ser (c.148C>T) is classified Benign in ODAD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0752); Rare (popmax 0.342%, nfe); Associated with primary ciliary dyskinesia 30.

What condition is associated with ODAD3 p.Pro50Ser (c.148C>T)?

ODAD3 p.Pro50Ser (c.148C>T) is associated with primary ciliary dyskinesia 30 (ClinVar).

How common is ODAD3 p.Pro50Ser (c.148C>T) in the general population?

ODAD3 p.Pro50Ser (c.148C>T) is rare (popmax 0.342%, nfe) (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 ODAD3 p.Pro50Ser (c.148C>T)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

ODAD3 p.Pro50Ser

c.148C>T · rs143295007 · VCV241942

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.342%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 30

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP -4.6
Regional constraint	o/e 1.04	unconstrained · MANE · 14 kb · p 0.23 · regional, not allelic
Overall
CADD	1.81	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.342% European (non-Finnish) · 4,036/1,180,036 alleles

Filtering AF 0.333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.33%

Overall 0.361% 5,833/1,614,184 alleles · rare exomes 5,238/1,461,848 · genomes 595/152,336 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.92%	52
Amishnot grpmax-eligible	0.877%	114
European (non-Finnish)grpmax	0.342%	292
Remaining individualsnot grpmax-eligible	0.331%	302
Admixed American	0.316%	316
Ashkenazi Jewishnot grpmax-eligible	0.155%	644
Middle Eastern	0.115%	866
South Asian	0.0812%	1,231
African / African-American	0.052%	1,924

Finnish 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: ODAD3
Protein: p.Pro50Ser
Coding: c.148C>T
MANE Select: NM_145045
dbSNP: rs143295007
Type: single nucleotide variant
Location: chr19:11434869 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.97 · 1 PDB
Residue 50: the 'disordered' region

Full ODAD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 30 — 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

ODAD3 c.964-1G>A Likely pathogenic ★★ same condition
ODAD3 p.Gln354Ter Pathogenic ★★ same condition
ODAD3 c.1435-5C>A Uncertain significance ★★ same condition
ODAD3 p.Ala203Pro Uncertain significance ★★ ⚠ same condition
ODAD3 p.Ala220Val Uncertain significance ★★ ⚠ same condition
ODAD3 p.Ala308Thr Uncertain significance ★★ ⚠ same condition
ODAD3 p.Ala341Ser Uncertain significance ★★ ⚠ same condition
ODAD3 p.Ala432Thr 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/odad3-p-pro50ser (accessed [today's date]).

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