Is RARB p.Pro433Arg (c.1298C>G) pathogenic?

RARB p.Pro433Arg (c.1298C>G) is classified Uncertain significance in RARB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). Very rare (popmax 0.00933%, afr); Associated with Inborn genetic diseases.

What condition is associated with RARB p.Pro433Arg (c.1298C>G)?

RARB p.Pro433Arg (c.1298C>G) is associated with Inborn genetic diseases (ClinVar).

How common is RARB p.Pro433Arg (c.1298C>G) in the general population?

RARB p.Pro433Arg (c.1298C>G) is very rare (popmax 0.00933%, afr) (gnomAD).

RARB p.Pro433Arg

c.1298C>G · VCV3430417

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00933%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.38	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 108 bp · p 0.11 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00933% African / African-American · 7/75,004 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.000496% 8/1,613,328 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00933%	10,715
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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: RARB
Protein: p.Pro433Arg
Coding: c.1298C>G
MANE Select: NM_000965
Type: single nucleotide variant
Location: chr3:25596567 (GRCh38)
Gene constraint: LOEUF 0.477 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 80.68 · 9 PDB
Residue 433: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RARB p.Leu407Pro Likely pathogenic ★★ same condition
RARB p.Gly216Ser Uncertain significance ★★ same condition
RARB p.Thr50Ala Uncertain significance ★★ same condition
RARB p.Arg119Gln Uncertain significance ★ same condition
RARB p.Arg360Gln Uncertain significance ★ same condition
RARB p.Gln14Glu Uncertain significance ★ same condition
RARB p.Gly282Val Uncertain significance ★ same condition
RARB p.Gly440Arg 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/rarb-p-pro433arg (accessed [today's date]).

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