Is RXRB p.Pro103Arg (c.308C>G) pathogenic?

RXRB p.Pro103Arg (c.308C>G) is classified Uncertain significance in RXRB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: likely benign (0.1075); Very rare (popmax 0.000524%, nfe).

How common is RXRB p.Pro103Arg (c.308C>G) in the general population?

RXRB p.Pro103Arg (c.308C>G) is very rare (popmax 0.000524%, nfe) (gnomAD).

What do computational predictors say about RXRB p.Pro103Arg (c.308C>G)?

AlphaMissense predicts likely benign (score 0.1075) — an in-silico prediction, not a clinical call.

RXRB p.Pro103Arg

c.308C>G · VCV3949007

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1075 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000524%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1075	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -10.32	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.3	GERP 0.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 2,123 bp · p 0.037 · regional, not allelic
Overall
CADD	22.0	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 0.000524% European (non-Finnish) · 5/954,312 alleles

Filtering AF 0.000154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000112%

Overall 0.000413% 5/1,210,468 alleles · very rare exomes 4/1,059,012 · genomes 1/151,456 · joint denominator

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: RXRB
Protein: p.Pro103Arg
Coding: c.308C>G
MANE Select: NM_021976
Type: single nucleotide variant
Location: chr6:33199344 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 72.81 · 7 PDB
Residue 103: the 'modulating' region; the 'disordered' region

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

Similar variants

RXRB p.Pro103Ser Uncertain significance ★ ⚠ same residue
RXRB c.235+1G>T Uncertain significance ★ same type
RXRB p.Ala274Val Uncertain significance ★ ⚠ same type
RXRB p.Ala292Pro Uncertain significance ★ ⚠ same type
RXRB p.Ala52Gly Uncertain significance ★ ⚠ same type
RXRB p.Ala54Gly Uncertain significance ★ ⚠ same type
RXRB p.Arg242Trp Uncertain significance ★ ⚠ same type
RXRB p.Arg25Gln Uncertain significance ★ ⚠ same type

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/rxrb-p-pro103arg (accessed [today's date]).

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