Is RBP3 p.Val593Met (c.1777G>A) pathogenic?

RBP3 p.Val593Met (c.1777G>A) is classified Uncertain significance in RBP3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-06). AlphaMissense: ambiguous (0.3842); Very rare (popmax 0.00223%, eas); Associated with inherited retinal dystrophy.

What condition is associated with RBP3 p.Val593Met (c.1777G>A)?

RBP3 p.Val593Met (c.1777G>A) is associated with inherited retinal dystrophy (ClinVar).

How common is RBP3 p.Val593Met (c.1777G>A) in the general population?

RBP3 p.Val593Met (c.1777G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about RBP3 p.Val593Met (c.1777G>A)?

AlphaMissense predicts ambiguous (score 0.3842) — an in-silico prediction, not a clinical call.

RBP3 p.Val593Met

c.1777G>A · rs782377821 · VCV1904856

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3842 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.3842	ambiguous
SaProt	LLR -8.86	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.4, phastCons 1
Overall
CADD	22.5	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 0.00223% East Asian · 1/44,890 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000435% 7/1,607,402 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
African / African-American	0.00133%	74,952
South Asian	0.0011%	91,086
European (non-Finnish)	0.000339%	294,983

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.Val593Met
Coding: c.1777G>A
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs782377821
Type: single nucleotide variant
Location: chr10:47350261 (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.Val593Leu Uncertain significance ★ same residue
RBP3 p.Val593Ala Uncertain significance 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-val593met (accessed [today's date]).

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