Is RBP3 p.Asp445His (c.1333G>C) pathogenic?

RBP3 p.Asp445His (c.1333G>C) is classified Conflicting classifications of pathogenicity in RBP3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-18). AlphaMissense: likely pathogenic (0.648); Rare (popmax 0.176%, eas); Associated with inherited retinal dystrophy.

What condition is associated with RBP3 p.Asp445His (c.1333G>C)?

RBP3 p.Asp445His (c.1333G>C) is associated with inherited retinal dystrophy (ClinVar).

How common is RBP3 p.Asp445His (c.1333G>C) in the general population?

RBP3 p.Asp445His (c.1333G>C) is rare (popmax 0.176%, eas) (gnomAD).

What do computational predictors say about RBP3 p.Asp445His (c.1333G>C)?

AlphaMissense predicts likely pathogenic (score 0.648) — an in-silico prediction, not a clinical call.

RBP3 p.Asp445His

c.1333G>C · rs569378041 · VCV761647

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.648 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.176%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.648	likely pathogenic
SaProt	LLR -8.44	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.4, phastCons 1
Overall
CADD	22.3	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 0.176% East Asian · 79/44,870 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.133%

Overall 0.00731% 118/1,613,288 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.176%	568
South Asian	0.0187%	5,358
Remaining individualsnot grpmax-eligible	0.0144%	6,945
Admixed American	0.00167%	60,028
European (non-Finnish)	0.00102%	98,336

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.Asp445His
Coding: c.1333G>C
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs569378041
Type: single nucleotide variant
Location: chr10:47349817 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB

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

Similar variants

RBP3 p.Asp445Asn Uncertain significance ★★ ⚠ same residue
RBP3 p.Asp445= Likely benign ★ same residue
RBP3 p.Gln141Ter Pathogenic/Likely pathogenic ★★ same condition
RBP3 p.Glu149Ter Pathogenic ★★ same condition
RBP3 p.Ala263Ser Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala325Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala546Val Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala570Val 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-asp445his (accessed [today's date]).

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