Is RXRG p.Ser291Phe (c.872C>T) pathogenic?

RXRG p.Ser291Phe (c.872C>T) is classified Uncertain significance in RXRG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.5645); Absent from gnomAD v4.1.

How common is RXRG p.Ser291Phe (c.872C>T) in the general population?

RXRG p.Ser291Phe (c.872C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RXRG p.Ser291Phe (c.872C>T)?

AlphaMissense predicts likely pathogenic (score 0.5645) — an in-silico prediction, not a clinical call.

RXRG p.Ser291Phe

c.872C>T · VCV4158387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5645 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5645	likely pathogenic
REVEL	0.911	moderately pathogenic-leaning
SaProt	LLR -14.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 19 kb · p 1.6e-13 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RXRG
Protein: p.Ser291Phe
Coding: c.872C>T
MANE Select: NM_006917
Type: single nucleotide variant
Location: chr1:165410743 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 75.28 · 2 PDB
Residue 291: the nr lbd domain; an α-helix

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

Similar variants

RXRG p.Ala272Thr Uncertain significance ★ ⚠ same type
RXRG p.Ala31Thr Uncertain significance ★ ⚠ same type
RXRG p.Ala52Val Uncertain significance ★ ⚠ same type
RXRG p.Arg217Gln Uncertain significance ★ ⚠ same type
RXRG p.Arg219Gly Uncertain significance ★ ⚠ same type
RXRG p.Arg286His Uncertain significance ★ ⚠ same type
RXRG p.Arg422Cys Uncertain significance ★ ⚠ same type
RXRG p.Arg71Gln 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/rxrg-p-ser291phe (accessed [today's date]).

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