Is RBP3 p.Pro413Ser (c.1237C>T) pathogenic?

RBP3 p.Pro413Ser (c.1237C>T) is classified Uncertain significance in RBP3 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-11-20). AlphaMissense: likely benign (0.0825); Very rare (popmax 0.00212%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with RBP3 p.Pro413Ser (c.1237C>T)?

RBP3 p.Pro413Ser (c.1237C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is RBP3 p.Pro413Ser (c.1237C>T) in the general population?

RBP3 p.Pro413Ser (c.1237C>T) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about RBP3 p.Pro413Ser (c.1237C>T)?

AlphaMissense predicts likely benign (score 0.0825) — an in-silico prediction, not a clinical call.

RBP3 p.Pro413Ser

c.1237C>T · rs782469310 · VCV224751

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0825 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0825	likely benign
SaProt	LLR -8.22	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 -0.49	GERP -3
Overall
CADD	6.765	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; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,180,014 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00178% 26/1,459,888 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,201
Remaining individualsnot grpmax-eligible	0.0016%	62,492

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.Pro413Ser
Coding: c.1237C>T
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs782469310
Type: single nucleotide variant
Location: chr10:47349721 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB
Residue 413: the 'transactivation' region; the 'rb1 binding' region

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

E2F1 p.Phe413= Likely benign same residue
RBP3 p.Gln141Ter Pathogenic/Likely pathogenic ★★ same condition
RBP3 p.Glu149Ter Pathogenic ★★ same condition
RBP3 p.Ala263Ser Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala325Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala546Val Uncertain significance ★★ same condition
RBP3 p.Ala570Val 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-pro413ser (accessed [today's date]).

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