Is RSPH9 p.Pro87Arg (c.260C>G) pathogenic?

RSPH9 p.Pro87Arg (c.260C>G) is classified Uncertain significance in RSPH9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). AlphaMissense: likely benign (0.1752); Very rare (popmax 0.00364%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with RSPH9 p.Pro87Arg (c.260C>G)?

RSPH9 p.Pro87Arg (c.260C>G) is associated with primary ciliary dyskinesia (ClinVar).

How common is RSPH9 p.Pro87Arg (c.260C>G) in the general population?

RSPH9 p.Pro87Arg (c.260C>G) is very rare (popmax 0.00364%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

What do computational predictors say about RSPH9 p.Pro87Arg (c.260C>G)?

AlphaMissense predicts likely benign (score 0.1752) — an in-silico prediction, not a clinical call.

RSPH9 p.Pro87Arg

c.260C>G · rs774989438 · VCV525281

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1752 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.1752	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 26 kb · p 0.58 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00364% European (non-Finnish) · 43/1,179,990 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00273% 44/1,613,626 alleles · very rare exomes 43/1,461,428 · genomes 1/152,198 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,442
Remaining individualsnot grpmax-eligible	0.0016%	62,434

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.Pro87Arg
Coding: c.260C>G
MANE Select: NM_152732
dbSNP: rs774989438
Type: single nucleotide variant
Location: chr6:43650407 (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.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
RSPH9 p.Arg240His 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-pro87arg (accessed [today's date]).

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