Is RBP3 p.Pro25Thr (c.73C>A) pathogenic?

RBP3 p.Pro25Thr (c.73C>A) is classified Uncertain significance in RBP3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-25). AlphaMissense: likely benign (0.1496); Ultra-rare (popmax 0.0507%, afr); Associated with Inborn genetic diseases.

What condition is associated with RBP3 p.Pro25Thr (c.73C>A)?

RBP3 p.Pro25Thr (c.73C>A) is associated with Inborn genetic diseases (ClinVar).

How common is RBP3 p.Pro25Thr (c.73C>A) in the general population?

RBP3 p.Pro25Thr (c.73C>A) is ultra-rare (popmax 0.0507%, afr) (gnomAD).

What do computational predictors say about RBP3 p.Pro25Thr (c.73C>A)?

AlphaMissense predicts likely benign (score 0.1496) — an in-silico prediction, not a clinical call.

RBP3 p.Pro25Thr

c.73C>A · rs142651412 · VCV1366166

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1496 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0507%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1496	likely benign
SaProt	LLR -5.18	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 1.1	GERP 0.61, phastCons 0.81
Overall
CADD	19.03	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 0.0507% African / African-American · 38/74,920 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0335%

Overall 0.00254% 41/1,612,522 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0507%	1,972
Middle Eastern	0.0164%	6,084
Admixed American	0.00333%	30,007

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.Pro25Thr
Coding: c.73C>A
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs142651412
Type: single nucleotide variant
Location: chr10:47348557 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RBP3 p.Pro25= Likely benign ★★ same residue
RBP3 p.Ala1224Ser Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala243Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala252Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala420Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala424Val Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala549Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala549Val 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-pro25thr (accessed [today's date]).

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