Is RBP3 p.Ala876Ser (c.2626G>T) pathogenic?

RBP3 p.Ala876Ser (c.2626G>T) is classified Conflicting classifications of pathogenicity in RBP3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.0874); Ultra-rare (popmax 0.0285%, sas); Associated with Inborn genetic diseases.

What condition is associated with RBP3 p.Ala876Ser (c.2626G>T)?

RBP3 p.Ala876Ser (c.2626G>T) is associated with Inborn genetic diseases, retinitis pigmentosa (ClinVar).

How common is RBP3 p.Ala876Ser (c.2626G>T) in the general population?

RBP3 p.Ala876Ser (c.2626G>T) is ultra-rare (popmax 0.0285%, sas) (gnomAD).

What do computational predictors say about RBP3 p.Ala876Ser (c.2626G>T)?

AlphaMissense predicts likely benign (score 0.0874) — an in-silico prediction, not a clinical call.

RBP3 p.Ala876Ser

c.2626G>T · rs138240045 · VCV299959

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0874 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0874	likely benign
SaProt	LLR -6.59	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 5.8	GERP 1.5, phastCons 1
Overall
CADD	13.52	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 0.0285% South Asian · 26/91,086 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.0273% 441/1,612,638 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.929%	108
Remaining individualsnot grpmax-eligible	0.102%	976
South Asiangrpmax	0.0285%	3,503
Middle Eastern	0.0164%	6,082
Admixed American	0.015%	6,668
European (non-Finnish)	0.00559%	17,880

Ashkenazi Jewish 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.Ala876Ser
Coding: c.2626G>T
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs138240045
Type: single nucleotide variant
Location: chr10:47351110 (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

Also linked: retinitis pigmentosa

Similar variants

RBP3 p.Ala876Thr Uncertain significance ★★ ⚠ 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.Ala263Ser Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala312Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala379Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala403Thr 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-ala876ser (accessed [today's date]).

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