Is RBP3 p.Thr866= (c.2598G>A) pathogenic?

RBP3 p.Thr866= (c.2598G>A) is classified Likely benign in RBP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-06). Very rare (popmax 0.00133%, afr).

How common is RBP3 p.Thr866= (c.2598G>A) in the general population?

RBP3 p.Thr866= (c.2598G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

RBP3 p.Thr866=

c.2598G>A · rs782000061 · VCV1536610

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3
Overall
CADD	0.523	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,936 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000682% 11/1,612,118 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00161%	62,252
African / African-Americangrpmax	0.00133%	74,936
South Asian	0.0011%	91,058
European (non-Finnish)	0.000678%	147,495

Finnish 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.Thr866=
Coding: c.2598G>A
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs782000061
Type: single nucleotide variant
Location: chr10:47351082 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB

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

Similar variants

RBP3 p.Thr866Met Uncertain significance ★★ ⚠ same residue
RBP3 p.Thr866Lys 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-thr866 (accessed [today's date]).

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