Is RBP3 p.Pro100Leu (c.299C>T) pathogenic?

RBP3 p.Pro100Leu (c.299C>T) is classified Conflicting classifications of pathogenicity in RBP3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-15). AlphaMissense: likely benign (0.0696); Rare (popmax 0.386%, afr).

How common is RBP3 p.Pro100Leu (c.299C>T) in the general population?

RBP3 p.Pro100Leu (c.299C>T) is rare (popmax 0.386%, afr) (gnomAD).

What do computational predictors say about RBP3 p.Pro100Leu (c.299C>T)?

AlphaMissense predicts likely benign (score 0.0696) — an in-silico prediction, not a clinical call.

RBP3 p.Pro100Leu

c.299C>T · rs143076262 · VCV597526

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0696 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.386%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0696	likely benign
SaProt	LLR -7.48	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	0.488	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 0.386% African / African-American · 290/75,046 alleles

Filtering AF 0.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.336%

Overall 0.0195% 315/1,613,734 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.386%	259
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.016%	6,250
Admixed American	0.0133%	7,504
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
European (non-Finnish)	0.000424%	236,007

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.Pro100Leu
Coding: c.299C>T
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.Pro100Arg Uncertain significance ★★ ⚠ same residue
RBP3 p.Pro100Gln Uncertain significance ★★ ⚠ 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-pro100leu (accessed [today's date]).

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