Is RBP3 p.Cys40= (c.120C>T) pathogenic?

RBP3 p.Cys40= (c.120C>T) is classified Conflicting classifications of pathogenicity in RBP3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-25). Ultra-rare (popmax 0.0323%, nfe); Associated with retinitis pigmentosa.

What condition is associated with RBP3 p.Cys40= (c.120C>T)?

RBP3 p.Cys40= (c.120C>T) is associated with retinitis pigmentosa (ClinVar).

How common is RBP3 p.Cys40= (c.120C>T) in the general population?

RBP3 p.Cys40= (c.120C>T) is ultra-rare (popmax 0.0323%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

RBP3 p.Cys40=

c.120C>T · rs373417235 · VCV722675

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0323%, nfe)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.62, phastCons 1
Overall
CADD	9.076	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0323% European (non-Finnish) · 381/1,180,048 alleles

Filtering AF 0.0296% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0285%

Overall 0.047% 758/1,613,366 alleles · ultra-rare exomes 643/1,461,148 · genomes 115/152,218 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.554%	180
Remaining individualsnot grpmax-eligible	0.0336%	2,975
European (non-Finnish)grpmax	0.0323%	3,097
Middle Eastern	0.0164%	6,084
Admixed American	0.00333%	30,003
African / African-American	0.00133%	74,944
South Asian	0.0011%	91,090

Finnish 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.Cys40=
Coding: c.120C>T
MANE Select: NM_002900
dbSNP: rs373417235
Type: single nucleotide variant
Location: chr10:47348604 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

RBP3 p.Cys40Gly Uncertain significance ★★ ⚠ same residue
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
RBP3 p.Ala688Val Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala803Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Arg170Gln 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-cys40 (accessed [today's date]).

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