Is RBP3 p.Arg86Cys (c.256C>T) pathogenic?

RBP3 p.Arg86Cys (c.256C>T) is classified Uncertain significance in RBP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-14). AlphaMissense: likely benign (0.254); Very rare (popmax 0.00801%, afr).

How common is RBP3 p.Arg86Cys (c.256C>T) in the general population?

RBP3 p.Arg86Cys (c.256C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about RBP3 p.Arg86Cys (c.256C>T)?

AlphaMissense predicts likely benign (score 0.254) — an in-silico prediction, not a clinical call.

RBP3 p.Arg86Cys

c.256C>T · rs782583157 · VCV1491082

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.254 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.254	likely benign
SaProt	LLR -13.32	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 1.5	GERP 1.6, phastCons 0.1
Overall
CADD	25.2	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 0.00801% African / African-American · 6/74,916 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00149% 24/1,613,500 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,486
South Asian	0.00549%	18,218
Remaining individualsnot grpmax-eligible	0.0048%	20,828
East Asian	0.00223%	44,888
Admixed American	0.00167%	60,014
Finnishnot grpmax-eligible	0.00158%	63,476
European (non-Finnish)	0.000593%	168,577

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.Arg86Cys
Coding: c.256C>T
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs782583157
Type: single nucleotide variant
Location: chr10:47348740 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB
Residue 86: the 'disordered' region; the 'cyclin a:cdk2 binding' region

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

Similar variants

RBP3 p.Arg86His Uncertain significance ★★ ⚠ same residue
RBP3 p.Arg86= Conflicting classifications of pathogenicity ★ same residue
RBP3 p.Arg388Ter Pathogenic ★★ same type
RBP3 p.Gln141Ter Pathogenic/Likely pathogenic ★★ same type
RBP3 p.Gln54Ter Pathogenic ★★ same type
RBP3 p.Glu149Ter Pathogenic ★★ same type
RBP3 p.Glu692Ter Pathogenic/Likely pathogenic ★★ same type
RBP3 p.Tyr784Ter Pathogenic/Likely pathogenic ★★ same type

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-arg86cys (accessed [today's date]).

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