Is RBP3 p.Pro348Ala (c.1042C>G) pathogenic?

RBP3 p.Pro348Ala (c.1042C>G) is classified Uncertain significance in RBP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-05). AlphaMissense: likely benign (0.1763); Absent from gnomAD v4.1.

How common is RBP3 p.Pro348Ala (c.1042C>G) in the general population?

RBP3 p.Pro348Ala (c.1042C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RBP3 p.Pro348Ala (c.1042C>G)?

AlphaMissense predicts likely benign (score 0.1763) — an in-silico prediction, not a clinical call.

RBP3 p.Pro348Ala

c.1042C>G · rs199720350 · VCV1367215

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1763 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1763	likely benign
SaProt	LLR -11.48	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 7.1	GERP 1.5, phastCons 1
Overall
CADD	23.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RBP3
Protein: p.Pro348Ala
Coding: c.1042C>G
MANE Select: NM_002900
dbSNP: rs199720350
Type: single nucleotide variant
Location: chr10:47349526 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB
Residue 348: the 'required for interaction with trim28' region; the 'disordered' region

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

Similar variants

RBP3 p.Pro348Ser Uncertain significance ★★ ⚠ same residue
RBP3 p.Pro348= 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-pro348ala (accessed [today's date]).

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