Is RBP3 p.Pro100Arg (c.299C>G) pathogenic?

RBP3 p.Pro100Arg (c.299C>G) is classified Uncertain significance in RBP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-21). AlphaMissense: likely benign (0.0573); Ultra-rare (popmax 0.0493%, mid).

How common is RBP3 p.Pro100Arg (c.299C>G) in the general population?

RBP3 p.Pro100Arg (c.299C>G) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about RBP3 p.Pro100Arg (c.299C>G)?

AlphaMissense predicts likely benign (score 0.0573) — an in-silico prediction, not a clinical call.

RBP3 p.Pro100Arg

c.299C>G · rs143076262 · VCV1052006

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0573 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0573	likely benign
SaProt	LLR -8.37	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 -1.7	GERP -3.3
Overall
CADD	0.012	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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.0026% 42/1,613,616 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
Remaining individualsnot grpmax-eligible	0.008%	12,495
European (non-Finnish)	0.00246%	40,691
East Asian	0.00223%	44,886
South Asian	0.0022%	45,543
Admixed American	0.00167%	60,012
African / African-American	0.00133%	74,924

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.Pro100Arg
Coding: c.299C>G
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs143076262
Type: single nucleotide variant
Location: chr10:47348783 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB
Residue 100: the 'cyclin a:cdk2 binding' region; the 'interaction with birc2/c-iap1' region

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

Similar variants

RBP3 p.Pro100Gln Uncertain significance ★★ ⚠ same residue
RBP3 p.Pro100Leu 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-pro100arg (accessed [today's date]).

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