Is RBP3 p.Arg388Ter (c.1162C>T) pathogenic?

RBP3 p.Arg388Ter (c.1162C>T) is classified Pathogenic in RBP3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-08-24). Very rare (popmax 0.000339%, nfe); Associated with RBP3-related disorder.

What condition is associated with RBP3 p.Arg388Ter (c.1162C>T)?

RBP3 p.Arg388Ter (c.1162C>T) is associated with RBP3-related disorder, retinitis pigmentosa 66 (ClinVar).

How common is RBP3 p.Arg388Ter (c.1162C>T) in the general population?

RBP3 p.Arg388Ter (c.1162C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

RBP3 p.Arg388Ter

c.1162C>T · rs782245537 · VCV978973

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

RBP3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.025	GERP -0.77, phastCons 0.012
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,016 alleles

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

Overall 0.000616% 9/1,459,996 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00643%	15,546
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)grpmax	0.000339%	295,004

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.Arg388Ter
Coding: c.1162C>T
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs782245537
Type: single nucleotide variant
Location: chr10:47349646 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB
Residue 388: the 'transactivation' region

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

Disease context

RBP3-related disorder

Also linked: retinitis pigmentosa 66

Similar variants

RBP3 p.Arg388Gln Uncertain significance ★★ ⚠ same residue
RBP3 p.Gln141Ter Pathogenic/Likely pathogenic ★★ same condition
RBP3 p.Gln54Ter 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.Ala325Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala379Thr 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-arg388ter (accessed [today's date]).

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