Is RORA p.Arg483Ter (c.1447C>T) pathogenic?

RORA p.Arg483Ter (c.1447C>T) is classified Conflicting classifications of pathogenicity in RORA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-04-30). Absent from gnomAD v4.1; Associated with intellectual developmental disorder with or without epilepsy or cerebellar ataxia.

How common is RORA p.Arg483Ter (c.1447C>T) in the general population?

RORA p.Arg483Ter (c.1447C>T) is absent from gnomAD v4.1 (gnomAD).

RORA p.Arg483Ter

Q: What condition is associated with RORA p.Arg483Ter (c.1447C>T)?

RORA p.Arg483Ter (c.1447C>T) is associated with intellectual developmental disorder with or without epilepsy or cerebellar ataxia (ClinVar).

c.1447C>T · rs2065199547 · VCV982776

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

intellectual developmental disorder with or without epilepsy or cerebellar ataxia

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 in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.32	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 10	GERP 5, phastCons 1
Overall
CADD	45.0	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

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: RORA
Protein: p.Arg483Ter
Coding: c.1447C>T
MANE Select: NM_134261
dbSNP: rs2065199547
Type: single nucleotide variant
Location: chr15:60497580 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.40 · 3 PDB
Residue 483: the nr lbd domain; an α-helix

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

Disease context

intellectual developmental disorder with or without epilepsy or cerebellar ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RORA p.Ala11Val Uncertain significance ★★ ⚠ same condition
RORA p.Ala7Ser Uncertain significance ★★ ⚠ same condition
RORA p.Arg170His Uncertain significance ★★ ⚠ same condition
RORA p.Arg462Gln Uncertain significance ★★ ⚠ same condition
RORA p.Arg47Thr Uncertain significance ★★ same condition
RORA p.Glu14Lys Uncertain significance ★★ ⚠ same condition
RORA p.His197Gln Uncertain significance ★★ ⚠ same condition
RORA p.Val268Met 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/rora-p-arg483ter (accessed [today's date]).

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