Is RXRB p.Pro104Ser (c.310C>T) pathogenic?

RXRB p.Pro104Ser (c.310C>T) is classified Likely benign in RXRB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-02-01). AlphaMissense: likely benign (0.0648); Ultra-rare (popmax 0.0285%, eas); Associated with RXRB-related disorder.

What condition is associated with RXRB p.Pro104Ser (c.310C>T)?

RXRB p.Pro104Ser (c.310C>T) is associated with RXRB-related disorder (ClinVar).

How common is RXRB p.Pro104Ser (c.310C>T) in the general population?

RXRB p.Pro104Ser (c.310C>T) is ultra-rare (popmax 0.0285%, eas) (gnomAD).

What do computational predictors say about RXRB p.Pro104Ser (c.310C>T)?

AlphaMissense predicts likely benign (score 0.0648) — an in-silico prediction, not a clinical call.

RXRB p.Pro104Ser

c.310C>T · rs201700806 · VCV3061577

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0648 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

RXRB-related disorder

Computational evidence

Protein change
AlphaMissense	0.0648	likely benign
REVEL	0.338	indeterminate
SaProt	LLR -5.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.3	GERP 0.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 2,123 bp · p 0.037 · regional, not allelic
Overall
CADD	15.41	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 0.0285% East Asian · 9/31,600 alleles

Filtering AF 0.0148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.011%

Overall 0.00711% 86/1,210,090 alleles · ultra-rare exomes 73/1,058,574 · genomes 13/151,516 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.155%	646
East Asiangrpmax	0.0285%	3,511
South Asian	0.00413%	24,236
European (non-Finnish)	0.000524%	190,727

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: RXRB
Protein: p.Pro104Ser
Coding: c.310C>T
MANE Select: NM_021976
dbSNP: rs201700806
Type: single nucleotide variant
Location: chr6:33199342 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 72.81 · 7 PDB
Residue 104: the 'modulating' region; the 'disordered' region

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

Disease context

RXRB-related disorder

Similar variants

RXRB c.16+9A>C Likely benign same condition
RXRB c.641-6C>G Benign same condition
RXRB p.Ala398= Likely benign same condition
RXRB p.Cys208= Benign same condition
RXRB p.His402= Likely benign same condition
RXRB p.Thr473= Likely benign same condition
RXRB c.235+1G>T Uncertain significance ★ same type
RXRB p.Ala274Val 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-pro104ser (accessed [today's date]).

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