Is RBP3 p.Pro467Ser (c.1399C>T) pathogenic?

RBP3 p.Pro467Ser (c.1399C>T) is classified Uncertain significance in RBP3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-09-07). AlphaMissense: likely benign (0.2608); Ultra-rare (popmax 0.0571%, sas); Associated with retinitis pigmentosa.

What condition is associated with RBP3 p.Pro467Ser (c.1399C>T)?

RBP3 p.Pro467Ser (c.1399C>T) is associated with retinitis pigmentosa (ClinVar).

How common is RBP3 p.Pro467Ser (c.1399C>T) in the general population?

RBP3 p.Pro467Ser (c.1399C>T) is ultra-rare (popmax 0.0571%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

What do computational predictors say about RBP3 p.Pro467Ser (c.1399C>T)?

AlphaMissense predicts likely benign (score 0.2608) — an in-silico prediction, not a clinical call.

RBP3 p.Pro467Ser

c.1399C>T · rs782195686 · VCV299982

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2608 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0571%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.2608	likely benign
SaProt	LLR -5.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 0.42, phastCons 0.99
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0571% South Asian · 52/91,082 alleles

Filtering AF 0.0447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0403%

Overall 0.00403% 65/1,613,062 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0571%	1,752
Remaining individualsnot grpmax-eligible	0.0112%	8,925
Admixed American	0.00667%	15,001
European (non-Finnish)	0.000169%	590,009

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: RBP3
Protein: p.Pro467Ser
Coding: c.1399C>T
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs782195686
Type: single nucleotide variant
Location: chr10:47349883 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB

Full RBP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

RBP3 p.Pro467Leu Uncertain significance ★★ ⚠ same residue
RBP3 p.Pro467= Likely benign ★★ same residue
RBP3 p.Ala263Ser Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala312Thr Uncertain significance ★★ same condition
RBP3 p.Ala379Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala403Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala688Val Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala803Thr 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/rbp3-p-pro467ser (accessed [today's date]).

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