Is SPAG1 p.Pro799= (c.2397G>A) pathogenic?

SPAG1 p.Pro799= (c.2397G>A) is classified Likely benign in SPAG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-03). Ultra-rare (popmax 0.0198%, sas); Associated with primary ciliary dyskinesia 28.

What condition is associated with SPAG1 p.Pro799= (c.2397G>A)?

SPAG1 p.Pro799= (c.2397G>A) is associated with primary ciliary dyskinesia 28, primary ciliary dyskinesia (ClinVar).

How common is SPAG1 p.Pro799= (c.2397G>A) in the general population?

SPAG1 p.Pro799= (c.2397G>A) is ultra-rare (popmax 0.0198%, sas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SPAG1 p.Pro799=

c.2397G>A · rs775891909 · VCV2175719

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, sas)

Conditions

primary ciliary dyskinesia 28

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 -3.4	GERP -4.3
Overall
CADD	0.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0198% South Asian · 18/91,076 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00564% 91/1,614,004 alleles · ultra-rare exomes 81/1,461,828 · genomes 10/152,176 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0198%	5,060
African / African-American	0.012%	8,324
European (non-Finnish)	0.00517%	19,345
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Admixed American	0.00167%	59,986

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: SPAG1
Protein: p.Pro799=
Coding: c.2397G>A
MANE Select: NM_003114
dbSNP: rs775891909
Type: single nucleotide variant
Location: chr8:100240519 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.50 · 4 PDB
Residue 799: the 'disordered' region

Full SPAG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 28 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

SPAG1 p.Pro799Leu Uncertain significance ★★ ⚠ same residue
SPAG1 c.1097-11C>G Pathogenic ★★ same condition
SPAG1 c.939+1G>A Likely pathogenic ★★ same condition
SPAG1 p.Arg697Ter Pathogenic ★★ same condition
SPAG1 p.Gln672Ter Pathogenic/Likely pathogenic ★★ same condition
SPAG1 p.Ala159Thr Uncertain significance ★★ ⚠ same condition
SPAG1 p.Ala159Val Uncertain significance ★★ ⚠ same condition
SPAG1 p.Ala642Thr 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/spag1-p-pro799 (accessed [today's date]).

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