Is RBP3 p.Arg530Ser (c.1588C>A) pathogenic?

RBP3 p.Arg530Ser (c.1588C>A) is classified Uncertain significance in RBP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely benign (0.1944); Very rare (popmax 0.00669%, eas); Associated with inherited retinal dystrophy.

What condition is associated with RBP3 p.Arg530Ser (c.1588C>A)?

RBP3 p.Arg530Ser (c.1588C>A) is associated with inherited retinal dystrophy (ClinVar).

How common is RBP3 p.Arg530Ser (c.1588C>A) in the general population?

RBP3 p.Arg530Ser (c.1588C>A) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about RBP3 p.Arg530Ser (c.1588C>A)?

AlphaMissense predicts likely benign (score 0.1944) — an in-silico prediction, not a clinical call.

RBP3 p.Arg530Ser

c.1588C>A · rs202162675 · VCV3028168

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1944 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1944	likely benign
SaProt	LLR -9.45	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 2.4	GERP 0.43, phastCons 0.11
Overall
CADD	11.78	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 0.00669% East Asian · 3/44,874 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000372% 6/1,612,990 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,958
South Asian	0.0011%	91,050
European (non-Finnish)	0.000169%	589,974

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.Arg530Ser
Coding: c.1588C>A
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs202162675
Type: single nucleotide variant
Location: chr10:47350072 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB

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

RBP3 p.Arg530Cys Uncertain significance ★★ ⚠ same residue
RBP3 p.Arg530His Uncertain significance ★ ⚠ 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

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-arg530ser (accessed [today's date]).

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