Is RSPH3 p.Asp130= (c.390T>C) pathogenic?

RSPH3 p.Asp130= (c.390T>C) is classified Likely benign in RSPH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-08). Very rare (popmax 8.55e-05%, nfe); Associated with primary ciliary dyskinesia 32.

What condition is associated with RSPH3 p.Asp130= (c.390T>C)?

RSPH3 p.Asp130= (c.390T>C) is associated with primary ciliary dyskinesia 32 (ClinVar).

How common is RSPH3 p.Asp130= (c.390T>C) in the general population?

RSPH3 p.Asp130= (c.390T>C) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

RSPH3 p.Asp130=

c.390T>C · rs1583708889 · VCV797880

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

Conditions

primary ciliary dyskinesia 32

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.35	GERP 2.9, phastCons 0.52
Overall
CADD	6.126	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.55e-05% European (non-Finnish) · 1/1,170,208 alleles

Overall 6.24e-05% 1/1,603,280 alleles · very rare exomes 1/1,450,940 · genomes 0/152,340 · joint denominator

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.Asp130=
Coding: c.390T>C
MANE Select: NM_031924
dbSNP: rs1583708889
Type: single nucleotide variant
Location: chr6:158983764 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 65.67 · 1 PDB

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-asp130 (accessed [today's date]).

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