Is RBP3 p.Ala263Ser (c.787G>T) pathogenic?

RBP3 p.Ala263Ser (c.787G>T) is classified Uncertain significance in RBP3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-28). AlphaMissense: likely benign (0.084); Rare (popmax 0.16%, eas); Associated with inherited retinal dystrophy.

What condition is associated with RBP3 p.Ala263Ser (c.787G>T)?

RBP3 p.Ala263Ser (c.787G>T) is associated with inherited retinal dystrophy, retinitis pigmentosa (ClinVar).

How common is RBP3 p.Ala263Ser (c.787G>T) in the general population?

RBP3 p.Ala263Ser (c.787G>T) is rare (popmax 0.16%, eas) (gnomAD).

What do computational predictors say about RBP3 p.Ala263Ser (c.787G>T)?

AlphaMissense predicts likely benign (score 0.084) — an in-silico prediction, not a clinical call.

RBP3 p.Ala263Ser

c.787G>T · rs77257977 · VCV299994

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.084 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.16%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.084	likely benign
SaProt	LLR -8.30	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 2.8	GERP 1.4, phastCons 1
Overall
CADD	16.89	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.16% East Asian · 72/44,874 alleles

Filtering AF 0.131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.12%

Overall 0.00446% 72/1,613,024 alleles · 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.Ala263Ser
Coding: c.787G>T
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs77257977
Type: single nucleotide variant
Location: chr10:47349271 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB
Residue 263: a β-strand; the 'required for interaction with trim28' region; the 'dimerization' region

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa

Similar variants

E2F1 p.Met263Leu Uncertain significance ★ ⚠ same residue
RBP3 p.Gln141Ter Pathogenic/Likely pathogenic ★★ same condition
RBP3 p.Glu149Ter Pathogenic ★★ same condition
RBP3 p.Ala312Thr Uncertain significance ★★ same condition
RBP3 p.Ala325Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala379Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala403Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala546Val 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-ala263ser (accessed [today's date]).

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