Is RORA p.Glu293fs (c.867_876dup) pathogenic?

RORA p.Glu293fs (c.867876dup) is classified Pathogenic in RORA (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-02). Absent from gnomAD; Associated with intellectual developmental disorder with or without epilepsy or cerebellar ataxia.

How common is RORA p.Glu293fs (c.867_876dup) in the general population?

RORA p.Glu293fs (c.867_876dup) is absent from gnomAD (gnomAD).

RORA p.Glu293fs

Q: What condition is associated with RORA p.Glu293fs (c.867_876dup)?

RORA p.Glu293fs (c.867_876dup) is associated with intellectual developmental disorder with or without epilepsy or cerebellar ataxia (ClinVar).

c.867_876dup · rs1595874842 · VCV807672

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 6 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 7.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RORA
Protein: p.Glu293fs
Coding: c.867_876dup
MANE Select: NM_134261
dbSNP: rs1595874842
Type: Duplication
Location: chr15:60505573 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.40 · 3 PDB
Residue 293: 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.Cys245fs Pathogenic ★ same condition
RORA p.Lys240_Pro241insSerTer Likely pathogenic ★ same condition
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

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-glu293fs (accessed [today's date]).

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