Is RSPH9 p.Pro245= (c.735G>A) pathogenic?

RSPH9 p.Pro245= (c.735G>A) is classified Conflicting classifications of pathogenicity in RSPH9 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-23). Ultra-rare (popmax 0.049%, eas); Associated with primary ciliary dyskinesia.

What condition is associated with RSPH9 p.Pro245= (c.735G>A)?

RSPH9 p.Pro245= (c.735G>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is RSPH9 p.Pro245= (c.735G>A) in the general population?

RSPH9 p.Pro245= (c.735G>A) is ultra-rare (popmax 0.049%, 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.Pro245=

c.735G>A · rs769469438 · VCV2042460

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.049%, eas)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.096	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -3.4
Overall
CADD	1.412	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.049% East Asian · 22/44,878 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.00409% 66/1,614,204 alleles · ultra-rare exomes 61/1,461,876 · genomes 5/152,328 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.049%	2,040
Middle Eastern	0.033%	3,030
Admixed American	0.00833%	12,006
Remaining individualsnot grpmax-eligible	0.008%	12,502
European (non-Finnish)	0.00254%	39,335
African / African-American	0.00133%	75,052
South Asian	0.0011%	91,082

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.Pro245=
Coding: c.735G>A
MANE Select: NM_152732
dbSNP: rs769469438
Type: single nucleotide variant
Location: chr6:43670853 (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 — 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

RSPH9 p.Pro245Leu Uncertain significance ★ ⚠ same residue
RSPH9 p.Arg156Ter Pathogenic ★★ same condition
RSPH9 p.Tyr39Ter Pathogenic ★★ 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-pro245 (accessed [today's date]).

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