Is RSPH9 p.Arg232= (c.696G>A) pathogenic?

RSPH9 p.Arg232= (c.696G>A) is classified Likely benign in RSPH9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-06). Very rare (popmax 0.00534%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with RSPH9 p.Arg232= (c.696G>A)?

RSPH9 p.Arg232= (c.696G>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is RSPH9 p.Arg232= (c.696G>A) in the general population?

RSPH9 p.Arg232= (c.696G>A) is very rare (popmax 0.00534%, afr) (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.Arg232=

c.696G>A · VCV3716186

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.034	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -3.4
Overall
CADD	0.524	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,938 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000434% 7/1,614,068 alleles · very rare exomes 5/1,461,860 · genomes 2/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,734
East Asian	0.00223%	44,888
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	8.47e-05%	1,180,045

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.Arg232=
Coding: c.696G>A
MANE Select: NM_152732
Type: single nucleotide variant
Location: chr6:43670814 (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-arg232 (accessed [today's date]).

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