Is RSPH1 p.Pro247= (c.741C>T) pathogenic?

RSPH1 p.Pro247= (c.741C>T) is classified Likely benign in RSPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-13). Ultra-rare (popmax 0.015%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with RSPH1 p.Pro247= (c.741C>T)?

RSPH1 p.Pro247= (c.741C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is RSPH1 p.Pro247= (c.741C>T) in the general population?

RSPH1 p.Pro247= (c.741C>T) is ultra-rare (popmax 0.015%, amr) (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.Pro247=

c.741C>T · rs142166675 · VCV703737

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

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 -4.2	GERP -4.3
Overall
CADD	0.239	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/59,934 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00186% 30/1,613,288 alleles · ultra-rare exomes 21/1,461,786 · genomes 9/151,502 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,659
Remaining individualsnot grpmax-eligible	0.0064%	15,619
African / African-American	0.00401%	24,909
European (non-Finnish)	0.00119%	84,274

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: RSPH1
Protein: p.Pro247=
Coding: c.741C>T
MANE Select: NM_080860
dbSNP: rs142166675
Type: single nucleotide variant
Location: chr21:42476034 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.95 · 1 PDB
Residue 247: the 'disordered' region

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-pro247 (accessed [today's date]).

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