Is RBP3 p.Pro1213Ser (c.3637C>T) pathogenic?

RBP3 p.Pro1213Ser (c.3637C>T) is classified Conflicting classifications of pathogenicity in RBP3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-15). AlphaMissense: likely pathogenic (0.6962); Very rare (popmax 0.004%, afr); Associated with RBP3-related disorder.

What condition is associated with RBP3 p.Pro1213Ser (c.3637C>T)?

RBP3 p.Pro1213Ser (c.3637C>T) is associated with RBP3-related disorder, inherited retinal dystrophy (ClinVar).

How common is RBP3 p.Pro1213Ser (c.3637C>T) in the general population?

RBP3 p.Pro1213Ser (c.3637C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about RBP3 p.Pro1213Ser (c.3637C>T)?

AlphaMissense predicts likely pathogenic (score 0.6962) — an in-silico prediction, not a clinical call.

RBP3 p.Pro1213Ser

c.3637C>T · rs782519239 · VCV865982

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.6962 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt

Conditions

RBP3-related disorder

Computational evidence

Protein change
AlphaMissense	0.6962	likely pathogenic
SaProt	LLR -12.47	damaging
⇒ AlphaMissense and SaProt both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 0.44, phastCons 1
Overall
CADD	23.7	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 0.004% African / African-American · 3/74,932 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00235% 38/1,614,010 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,977
European (non-Finnish)	0.00288%	34,707
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Pro1213Ser
Coding: c.3637C>T
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs782519239
Type: single nucleotide variant
Location: chr10:47357350 (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

Also linked: inherited retinal dystrophy

Similar variants

RBP3 p.Pro1213Thr Uncertain significance ★ ⚠ same residue
RBP3 p.Arg388Ter Pathogenic ★★ same condition
RBP3 p.Gln141Ter Pathogenic/Likely pathogenic ★★ same condition
RBP3 p.Glu149Ter Pathogenic ★★ same condition
RBP3 p.Glu692Ter Pathogenic/Likely pathogenic ★★ same condition
RBP3 p.Tyr784Ter Pathogenic/Likely pathogenic ★★ same condition
RBP3 p.Tyr841Ter Pathogenic/Likely pathogenic ★★ same condition
RBP3 p.Ala263Ser 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-pro1213ser (accessed [today's date]).

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