Is RSPH9 p.Pro273= (c.819C>T) pathogenic?

RSPH9 p.Pro273= (c.819C>T) is classified Conflicting classifications of pathogenicity in RSPH9 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-22). Rare (popmax 0.927%, eas); Associated with primary ciliary dyskinesia 12.

What condition is associated with RSPH9 p.Pro273= (c.819C>T)?

RSPH9 p.Pro273= (c.819C>T) is associated with primary ciliary dyskinesia 12, primary ciliary dyskinesia (ClinVar).

How common is RSPH9 p.Pro273= (c.819C>T) in the general population?

RSPH9 p.Pro273= (c.819C>T) is rare (popmax 0.927%, eas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

RSPH9 p.Pro273=

c.819C>T · rs79412180 · VCV357020

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.927%, eas)

Conditions

primary ciliary dyskinesia 12

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.184	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -0.56, phastCons 0.98
Overall
CADD	8.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.927% East Asian · 416/44,878 alleles

Filtering AF 0.853% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.824%

Overall 0.0263% 424/1,614,184 alleles · rare exomes 388/1,461,860 · genomes 36/152,324 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.927%	108
Remaining individualsnot grpmax-eligible	0.0128%	7,814

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: RSPH9
Protein: p.Pro273=
Coding: c.819C>T
MANE Select: NM_152732
dbSNP: rs79412180
Type: single nucleotide variant
Location: chr6:43670937 (GRCh38)
Gene constraint: LOEUF 1.316 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.03 · 1 PDB

Full RSPH9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 12 — 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

RSPH9 p.Arg156Ter Pathogenic ★★ same condition
RSPH9 p.Tyr39Ter Pathogenic ★★ same condition
RSPH9 c.228-10T>G Uncertain significance ★★ same condition
RSPH9 p.Ala150Val Uncertain significance ★★ ⚠ same condition
RSPH9 p.Ala94Val Uncertain significance ★★ ⚠ same condition
RSPH9 p.Arg139Cys Uncertain significance ★★ ⚠ same condition
RSPH9 p.Arg139His Uncertain significance ★★ same condition
RSPH9 p.Arg240Cys 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/rsph9-p-pro273 (accessed [today's date]).

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