Is RBP3 p.Phe359Ser (c.1076T>C) pathogenic?

RBP3 p.Phe359Ser (c.1076T>C) is classified Uncertain significance in RBP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-06). AlphaMissense: ambiguous (0.5378); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with RBP3 p.Phe359Ser (c.1076T>C)?

RBP3 p.Phe359Ser (c.1076T>C) is associated with Inborn genetic diseases (ClinVar).

How common is RBP3 p.Phe359Ser (c.1076T>C) in the general population?

RBP3 p.Phe359Ser (c.1076T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about RBP3 p.Phe359Ser (c.1076T>C)?

AlphaMissense predicts ambiguous (score 0.5378) — an in-silico prediction, not a clinical call.

RBP3 p.Phe359Ser

c.1076T>C · rs1380418518 · VCV1043986

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5378 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5378	ambiguous
SaProt	LLR -8.76	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP -0.92, phastCons 1
Overall
CADD	23.6	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 0.00167% Admixed American · 1/60,010 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00031% 5/1,612,840 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,240
Admixed Americangrpmax	0.00167%	60,010
European (non-Finnish)	0.000169%	589,998

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe359Ser
Coding: c.1076T>C
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs1380418518
Type: single nucleotide variant
Location: chr10:47349560 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB
Residue 359: the 'required for interaction with trim28' region

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.Phe359Leu Uncertain significance ★ ⚠ same residue
RBP3 p.Phe359= 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

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-phe359ser (accessed [today's date]).

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