Is RPGR p.Pro392= (c.1176G>A) pathogenic?

RPGR p.Pro392= (c.1176G>A) is classified Likely benign in RPGR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-20). Ultra-rare (popmax 0.0123%, sas); Associated with primary ciliary dyskinesia.

What condition is associated with RPGR p.Pro392= (c.1176G>A)?

RPGR p.Pro392= (c.1176G>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is RPGR p.Pro392= (c.1176G>A) in the general population?

RPGR p.Pro392= (c.1176G>A) is ultra-rare (popmax 0.0123%, sas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

RPGR p.Pro392=

c.1176G>A · rs149742786 · VCV2888613

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, sas)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.009	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.003	GERP -2.5
Overall
CADD	1.826	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0123% South Asian · 7/56,806 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00408%

Overall 0.00149% 18/1,209,783 alleles · ultra-rare exomes 17/1,097,960 · genomes 1/111,823 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0123%	8,115
Ashkenazi Jewishnot grpmax-eligible	0.00454%	22,028
African / African-American	0.0035%	28,605
East Asian	0.00296%	33,781
Remaining individualsnot grpmax-eligible	0.0021%	47,612
European (non-Finnish)	0.00067%	149,185

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: RPGR
Protein: p.Pro392=
Coding: c.1176G>A
MANE Select: NM_001034853
dbSNP: rs149742786
Type: single nucleotide variant
Location: chrX:38299025 (GRCh38)
Structure: AlphaFold pLDDT 56.59 · 3 PDB

Full RPGR 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

RPGR p.Pro392Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
RPGR c.1245+3A>G Pathogenic ★★★ same condition
RPGR c.1572+1G>A Pathogenic ★★★ same condition
RPGR c.1573-1G>A Pathogenic ★★★ same condition
RPGR c.1573-8A>G Likely pathogenic ★★★ same condition
RPGR c.1754-3C>G Pathogenic ★★★ same condition
RPGR c.247+5G>A Pathogenic ★★★ same condition
RPGR c.310+1G>C Pathogenic ★★★ 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/rpgr-p-pro392 (accessed [today's date]).

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