Is RPGR p.Ser152Pro (c.454T>C) pathogenic?

RPGR p.Ser152Pro (c.454T>C) is classified Uncertain significance in RPGR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-14). AlphaMissense: likely pathogenic (0.9938); Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia.

What condition is associated with RPGR p.Ser152Pro (c.454T>C)?

RPGR p.Ser152Pro (c.454T>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is RPGR p.Ser152Pro (c.454T>C) in the general population?

RPGR p.Ser152Pro (c.454T>C) 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.

What do computational predictors say about RPGR p.Ser152Pro (c.454T>C)?

AlphaMissense predicts likely pathogenic (score 0.9938) — an in-silico prediction, not a clinical call.

RPGR p.Ser152Pro

c.454T>C · rs2519894426 · VCV2814136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9938 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.9938	likely pathogenic · top 1% in RPGR
REVEL	0.899	moderately pathogenic-leaning
SaProt	LLR -12.68	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

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: RPGR
Protein: p.Ser152Pro
Coding: c.454T>C
MANE Select: NM_001034853
dbSNP: rs2519894426
Type: single nucleotide variant
Location: chrX:38318844 (GRCh38)
Structure: AlphaFold pLDDT 56.59 · 3 PDB
Residue 152: a UniProt-annotated variant site (in rp3); 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.Ser152Leu Likely pathogenic ★ same residue
RPGR p.Ser152Ter Likely pathogenic ★ 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

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-ser152pro (accessed [today's date]).

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