Is RSPH3 p.Pro13Arg (c.38C>G) pathogenic?

RSPH3 p.Pro13Arg (c.38C>G) is classified Benign in RSPH3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.1091); Common (popmax 15.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia 32.

What condition is associated with RSPH3 p.Pro13Arg (c.38C>G)?

RSPH3 p.Pro13Arg (c.38C>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.

What do computational predictors say about RSPH3 p.Pro13Arg (c.38C>G)?

AlphaMissense predicts likely benign (score 0.1091) — an in-silico prediction, not a clinical call.

RSPH3 p.Pro13Arg

Q: How common is RSPH3 p.Pro13Arg (c.38C>G) in the general population?

RSPH3 p.Pro13Arg (c.38C>G) is common (popmax 15.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.38C>G · rs61750776 · VCV475833

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1091 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 15.5%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 32

Computational evidence

Protein change
AlphaMissense	0.1091	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.33	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 1.7	GERP -1.5, phastCons 0.003
Regional constraint	o/e 0.94	unconstrained · MANE · 22 kb · p 0.2 · regional, not allelic
Overall
CADD	14.23	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P155R vs ClinVar P13R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.5% African / African-American · 11,444/73,776 alleles

Filtering AF 15.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.2%

Overall 0.831% 13,023/1,566,622 alleles · common exomes 6,329/1,414,450 · genomes 6,694/152,172 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	15.5%	6
Middle Eastern	1.1%	91
Admixed American	1.07%	94
Remaining individualsnot grpmax-eligible	1.06%	94
Ashkenazi Jewishnot grpmax-eligible	0.0373%	2,683
South Asian	0.0269%	3,717
European (non-Finnish)	0.0214%	4,664

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.Pro13Arg
Coding: c.38C>G
MANE Select: NM_031924
dbSNP: rs61750776
Type: single nucleotide variant
Location: chr6:158999513 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 65.67 · 1 PDB
Residue 155 UniProt numbering: the 'disordered' region

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-pro13arg (accessed [today's date]).

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