Is RBP3 p.Val1119fs (c.3354dup) pathogenic?

RBP3 p.Val1119fs (c.3354dup) is classified Likely pathogenic in RBP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). Very rare (popmax 0.00223%, eas); Associated with RBP3-related disorder.

What condition is associated with RBP3 p.Val1119fs (c.3354dup)?

RBP3 p.Val1119fs (c.3354dup) is associated with RBP3-related disorder (ClinVar).

How common is RBP3 p.Val1119fs (c.3354dup) in the general population?

RBP3 p.Val1119fs (c.3354dup) is very rare (popmax 0.00223%, eas) (gnomAD).

RBP3 p.Val1119fs

c.3354dup · rs781793052 · VCV2630148

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

RBP3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.5	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,882 alleles

Overall 6.84e-05% 1/1,461,884 alleles · very rare

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.Val1119fs
Coding: c.3354dup
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs781793052
Type: Duplication
Location: chr10:47355483 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB

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

Disease context

RBP3-related disorder

Similar variants

RBP3 p.Thr563fs Pathogenic/Likely pathogenic ★★ same condition
RBP3 p.Asn158fs Likely pathogenic ★ same condition
RBP3 p.Gln659fs Likely pathogenic ★ same condition
RBP3 p.Ser886fs Likely pathogenic ★ same condition
RBP3 p.Val1119Ala Uncertain significance ★ ⚠ same residue
RBP3 c.3245+1del Likely pathogenic ★★ same condition
RBP3 p.Arg388Ter Pathogenic ★★ same condition
RBP3 p.Asp427fs Pathogenic/Likely pathogenic ★★ 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-val1119fs (accessed [today's date]).

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