Is RBP3 p.Arg674Cys (c.2020C>T) pathogenic?

RBP3 p.Arg674Cys (c.2020C>T) is classified Uncertain significance in RBP3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-10-01). AlphaMissense: likely benign (0.1404); Ultra-rare (popmax 0.0117%, amr); Associated with inherited retinal dystrophy.

What condition is associated with RBP3 p.Arg674Cys (c.2020C>T)?

RBP3 p.Arg674Cys (c.2020C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is RBP3 p.Arg674Cys (c.2020C>T) in the general population?

RBP3 p.Arg674Cys (c.2020C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about RBP3 p.Arg674Cys (c.2020C>T)?

AlphaMissense predicts likely benign (score 0.1404) — an in-silico prediction, not a clinical call.

RBP3 p.Arg674Cys

c.2020C>T · rs782227889 · VCV1479282

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1404 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1404	likely benign
SaProt	LLR -10.66	damaging
⇒ SaProt calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.88	GERP -0.75, phastCons 1
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,008 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00149% 24/1,612,710 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,573
African / African-American	0.004%	24,979
South Asian	0.0022%	45,542
European (non-Finnish)	0.00102%	98,337

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.Arg674Cys
Coding: c.2020C>T
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs782227889
Type: single nucleotide variant
Location: chr10:47350504 (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.Arg674His 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
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-arg674cys (accessed [today's date]).

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