Is SPAG1 p.Ser347= (c.1041C>T) pathogenic?

SPAG1 p.Ser347= (c.1041C>T) is classified Likely benign in SPAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-30). Ultra-rare (popmax 0.0112%, eas); Associated with primary ciliary dyskinesia 28.

What condition is associated with SPAG1 p.Ser347= (c.1041C>T)?

SPAG1 p.Ser347= (c.1041C>T) is associated with primary ciliary dyskinesia 28 (ClinVar).

How common is SPAG1 p.Ser347= (c.1041C>T) in the general population?

SPAG1 p.Ser347= (c.1041C>T) is ultra-rare (popmax 0.0112%, eas) (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.Ser347=

c.1041C>T · rs762987978 · VCV2917953

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

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 -7.8	GERP -5
Overall
CADD	0.682	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% East Asian · 5/44,780 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000808% 13/1,608,158 alleles · ultra-rare exomes 11/1,459,262 · genomes 2/148,896 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,956
Admixed American	0.00336%	29,739
Remaining individualsnot grpmax-eligible	0.0016%	62,310
European (non-Finnish)	0.000425%	235,309

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.Ser347=
Coding: c.1041C>T
MANE Select: NM_003114
dbSNP: rs762987978
Type: single nucleotide variant
Location: chr8:100194213 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.50 · 4 PDB
Residue 347: the 'disordered' region; a modified residue (phosphoserine)

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

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

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
SPAG1 p.Arg132His 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-ser347 (accessed [today's date]).

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