Is RBP3 p.Pro594Arg (c.1781C>G) pathogenic?

RBP3 p.Pro594Arg (c.1781C>G) is classified Uncertain significance in RBP3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-21). AlphaMissense: likely pathogenic (0.9191); Ultra-rare (popmax 0.0151%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RBP3 p.Pro594Arg (c.1781C>G)?

RBP3 p.Pro594Arg (c.1781C>G) is associated with Inborn genetic diseases (ClinVar).

How common is RBP3 p.Pro594Arg (c.1781C>G) in the general population?

RBP3 p.Pro594Arg (c.1781C>G) is ultra-rare (popmax 0.0151%, nfe) (gnomAD).

What do computational predictors say about RBP3 p.Pro594Arg (c.1781C>G)?

AlphaMissense predicts likely pathogenic (score 0.9191) — an in-silico prediction, not a clinical call.

RBP3 p.Pro594Arg

c.1781C>G · rs781947747 · VCV839882

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9191 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0151%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9191	likely pathogenic
SaProt	LLR -14.66	damaging
⇒ AlphaMissense and SaProt both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 1.4, phastCons 1
Overall
CADD	23.2	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; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0151% European (non-Finnish) · 178/1,179,928 alleles

Filtering AF 0.0132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0125%

Overall 0.0114% 184/1,607,432 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0151%	6,629
Remaining individualsnot grpmax-eligible	0.00801%	12,486
African / African-American	0.00133%	74,946

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.Pro594Arg
Coding: c.1781C>G
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs781947747
Type: single nucleotide variant
Location: chr10:47350265 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RBP3 p.Pro594Leu Uncertain significance ★ ⚠ same residue
RBP3 p.Pro594= Likely benign ★★ same residue
RBP3 p.Pro594Ala Uncertain significance ★ ⚠ same residue
RBP3 p.Ala1224Ser Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala243Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala252Thr Uncertain significance ★★ same condition
RBP3 p.Ala420Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala424Val 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-pro594arg (accessed [today's date]).

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