Is RSPH3 p.Ser3= (c.9A>G) pathogenic?

RSPH3 p.Ser3= (c.9A>G) is classified Benign in RSPH3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 46%, amr) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia 32.

What condition is associated with RSPH3 p.Ser3= (c.9A>G)?

RSPH3 p.Ser3= (c.9A>G) is associated with primary ciliary dyskinesia 32 (ClinVar).

How is Primary ciliary dyskinesia inherited?

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

RSPH3 p.Ser3=

Q: How common is RSPH3 p.Ser3= (c.9A>G) in the general population?

RSPH3 p.Ser3= (c.9A>G) is common (popmax 46%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.9A>G · rs10945587 · VCV1165004

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 46%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

primary ciliary dyskinesia 32

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 0.25	GERP -3.7, phastCons 0.002
Overall
CADD	5.687	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 46% Admixed American · 27,151/59,006 alleles

Filtering AF 45.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 45.4%

Overall 16.8% 267,877/1,598,204 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	46%	2
East Asian	45.9%	2
African / African-American	40.2%	2
South Asian	20.9%	5
Remaining individualsnot grpmax-eligible	18.3%	5
Middle Eastern	18.1%	6
Amishnot grpmax-eligible	15.1%	7
Finnishnot grpmax-eligible	14%	7
Ashkenazi Jewishnot grpmax-eligible	12.6%	8
European (non-Finnish)	12.5%	8

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: RSPH3
Protein: p.Ser3=
Coding: c.9A>G
MANE Select: NM_031924
dbSNP: rs10945587
Type: single nucleotide variant
Location: chr6:158999542 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 65.67 · 1 PDB

Full RSPH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 32 — 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

RSPH3 c.205-2A>G Pathogenic ★★ same condition
RSPH3 c.859+1G>T Pathogenic/Likely pathogenic ★★ same condition
RSPH3 c.-95G>A Pathogenic ★★ same condition
RSPH3 p.Gln94Ter Likely pathogenic ★★ same condition
RSPH3 c.859+5G>A Uncertain significance ★★ same condition
RSPH3 c.-10G>T Uncertain significance ★★ ⚠ same condition
RSPH3 c.-120C>A Uncertain significance ★★ ⚠ same condition
RSPH3 c.-185G>A 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/rsph3-p-ser3 (accessed [today's date]).

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