Is RPGR p.Pro367Ser (c.1099C>T) pathogenic?

RPGR p.Pro367Ser (c.1099C>T) is classified Uncertain significance in RPGR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-19). AlphaMissense: likely benign (0.17); Very rare (popmax 0.00173%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with RPGR p.Pro367Ser (c.1099C>T)?

RPGR p.Pro367Ser (c.1099C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is RPGR p.Pro367Ser (c.1099C>T) in the general population?

RPGR p.Pro367Ser (c.1099C>T) is very rare (popmax 0.00173%, afr) (gnomAD).

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 RPGR p.Pro367Ser (c.1099C>T)?

AlphaMissense predicts likely benign (score 0.17) — an in-silico prediction, not a clinical call.

RPGR p.Pro367Ser

c.1099C>T · rs769641256 · VCV2050801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.17 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00173%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.17	likely benign
REVEL	0.283	benign-leaning
SaProt	LLR -11.91	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00173% African / African-American · 1/57,842 alleles

Filtering AF 0.000715% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000564%

Overall 0.00107% 13/1,211,547 alleles · very rare exomes 13/1,097,816 · genomes 0/113,731 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00173%	57,842
European (non-Finnish)	0.00134%	74,615

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.Pro367Ser
Coding: c.1099C>T
MANE Select: NM_001034853
dbSNP: rs769641256
Type: single nucleotide variant
Location: chrX:38299102 (GRCh38)
Structure: AlphaFold pLDDT 56.59 · 3 PDB
Residue 367: a β-strand

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.Pro367Ala Likely benign ★★★ ⚠ same residue
RPGR p.Pro367fs Pathogenic ★★★ same residue
RPGR p.Pro367del Uncertain significance ★★ 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

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-pro367ser (accessed [today's date]).

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