Is RORA c.1075+2del pathogenic?

RORA c.1075+2del is classified Likely pathogenic in RORA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). Associated with intellectual developmental disorder with or without epilepsy or cerebellar ataxia.

RORA c.1075+2del

Q: What condition is associated with RORA c.1075+2del?

RORA c.1075+2del is associated with intellectual developmental disorder with or without epilepsy or cerebellar ataxia (ClinVar).

VCV4277261

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

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	canonical splice-site (±1/±2)	predicted loss-of-function in a LoF-intolerant gene
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 2.7, phastCons 1
Non-coding constraint	Z 2.90	1 kb window · o/e 0.80 · regional · uncalibrated

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

Variant & gene context

Gene: RORA
Coding: c.1075+2del
MANE Select: NM_134261
Type: Deletion
Location: chr15:60503533 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.40 · 3 PDB

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.Asn187fs Likely pathogenic ★ same condition
RORA p.Gln332_Tyr333insTer Likely pathogenic ★ same condition
RORA p.Ile449fs Likely pathogenic ★ same condition
RORA c.1183+7_1183+10del Uncertain significance ★ same condition
RORA c.196+51382_196+51385del Conflicting classifications of pathogenicity ★ same condition
RORA p.Arg340fs Pathogenic/Likely pathogenic same condition
RORA p.Ala11Val Uncertain significance ★★ ⚠ same condition
RORA p.Ala7Ser 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-c-1075-plus-2del (accessed [today's date]).

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