Is RBP3 p.Ser356Arg (c.1068C>G) pathogenic?

RBP3 p.Ser356Arg (c.1068C>G) is classified Conflicting classifications of pathogenicity in RBP3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-08-16). AlphaMissense: likely benign (0.2083); Rare (popmax 0.145%, sas); Associated with inherited retinal dystrophy.

What condition is associated with RBP3 p.Ser356Arg (c.1068C>G)?

RBP3 p.Ser356Arg (c.1068C>G) is associated with inherited retinal dystrophy (ClinVar).

How common is RBP3 p.Ser356Arg (c.1068C>G) in the general population?

RBP3 p.Ser356Arg (c.1068C>G) is rare (popmax 0.145%, sas) (gnomAD).

What do computational predictors say about RBP3 p.Ser356Arg (c.1068C>G)?

AlphaMissense predicts likely benign (score 0.2083) — an in-silico prediction, not a clinical call.

RBP3 p.Ser356Arg

c.1068C>G · rs532818776 · VCV843897

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2083 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.145%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.2083	likely benign
SaProt	LLR -7.57	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 0.84	GERP 0.42, phastCons 0.32
Overall
CADD	19.64	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.145% South Asian · 132/91,084 alleles

Filtering AF 0.125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.117%

Overall 0.00887% 143/1,613,070 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.145%	690
Remaining individualsnot grpmax-eligible	0.0112%	8,929
European (non-Finnish)	0.000339%	295,004

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.Ser356Arg
Coding: c.1068C>G
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs532818776
Type: single nucleotide variant
Location: chr10:47349552 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB
Residue 356: the 'required for interaction with trim28' 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

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
RBP3 p.Ala830Thr 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-ser356arg (accessed [today's date]).

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