Is ODAD3 p.Phe58Ser (c.173T>C) pathogenic?

ODAD3 p.Phe58Ser (c.173T>C) is classified Benign in ODAD3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.0844); Low-frequency (popmax 1.48%, nfe); Associated with primary ciliary dyskinesia 30.

What condition is associated with ODAD3 p.Phe58Ser (c.173T>C)?

ODAD3 p.Phe58Ser (c.173T>C) is associated with primary ciliary dyskinesia 30 (ClinVar).

How common is ODAD3 p.Phe58Ser (c.173T>C) in the general population?

ODAD3 p.Phe58Ser (c.173T>C) is low-frequency (popmax 1.48%, 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.Phe58Ser (c.173T>C)?

AlphaMissense predicts likely benign (score 0.0844) — an in-silico prediction, not a clinical call.

ODAD3 p.Phe58Ser

c.173T>C · rs61741137 · VCV221005

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0844 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.48%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 30

Computational evidence

Protein change
AlphaMissense	0.0844	likely benign
REVEL	0.002	strongly benign-leaning
SaProt	LLR -3.67	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 -0.6	GERP -4.6
Regional constraint	o/e 1.04	unconstrained · MANE · 14 kb · p 0.23 · regional, not allelic
Overall
CADD	3.076	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 1.48% European (non-Finnish) · 17,433/1,180,022 alleles

Filtering AF 1.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.45%

Overall 1.22% 19,675/1,614,158 alleles · low-frequency exomes 18,553/1,461,872 · genomes 1,122/152,286 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.48%	68
Remaining individualsnot grpmax-eligible	1.03%	98
Amishnot grpmax-eligible	0.877%	114
South Asian	0.772%	130
Finnishnot grpmax-eligible	0.517%	193
Admixed American	0.463%	216
Ashkenazi Jewishnot grpmax-eligible	0.351%	285
Middle Eastern	0.231%	433
African / African-American	0.212%	472
East Asian	0.00892%	11,217

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.Phe58Ser
Coding: c.173T>C
MANE Select: NM_145045
dbSNP: rs61741137
Type: single nucleotide variant
Location: chr19:11434844 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.97 · 1 PDB
Residue 58: 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-phe58ser (accessed [today's date]).

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