Is RSPH1 p.Asp97= (c.291C>T) pathogenic?

RSPH1 p.Asp97= (c.291C>T) is classified Likely benign in RSPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia.

What condition is associated with RSPH1 p.Asp97= (c.291C>T)?

RSPH1 p.Asp97= (c.291C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is RSPH1 p.Asp97= (c.291C>T) in the general population?

RSPH1 p.Asp97= (c.291C>T) is absent from gnomAD v4.1 (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

RSPH1 p.Asp97=

c.291C>T · VCV3719249

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

primary ciliary dyskinesia

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 7.2	GERP 2.5, phastCons 1
Overall
CADD	6.367	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RSPH1
Protein: p.Asp97=
Coding: c.291C>T
MANE Select: NM_080860
Type: single nucleotide variant
Location: chr21:42486445 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.95 · 1 PDB

Full RSPH1 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

RSPH1 c.275-2A>C Pathogenic ★★ same condition
RSPH1 p.Leu188Ter Pathogenic/Likely pathogenic ★★ same condition
RSPH1 p.Trp94Ter Pathogenic/Likely pathogenic ★★ same condition
RSPH1 p.Ala131Thr Uncertain significance ★★ ⚠ same condition
RSPH1 p.Ala218Thr Uncertain significance ★★ ⚠ same condition
RSPH1 p.Ala218Val Uncertain significance ★★ ⚠ same condition
RSPH1 p.Ala238Pro Uncertain significance ★★ ⚠ same condition
RSPH1 p.Ala238Thr 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/rsph1-p-asp97 (accessed [today's date]).

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