Is RORA p.Ile449fs (c.1345del) pathogenic?

RORA p.Ile449fs (c.1345del) is classified Likely pathogenic in RORA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). No gnomAD frequency available for this variant; Associated with intellectual developmental disorder with or without epilepsy or cerebellar ataxia.

How common is RORA p.Ile449fs (c.1345del) in the general population?

RORA p.Ile449fs (c.1345del) is no gnomAD frequency available for this variant (gnomAD).

RORA p.Ile449fs

Q: What condition is associated with RORA p.Ile449fs (c.1345del)?

RORA p.Ile449fs (c.1345del) is associated with intellectual developmental disorder with or without epilepsy or cerebellar ataxia (ClinVar).

c.1345del · rs2541965807 · VCV3236192

Likely pathogenic Single submitter

Classification

Likely 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 10 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 5, 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.Ile449fs
Coding: c.1345del
MANE Select: NM_134261
dbSNP: rs2541965807
Type: Deletion
Location: chr15:60499954 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.40 · 3 PDB
Residue 449: 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 c.1075+2del Likely pathogenic ★ same condition
RORA p.Asn187fs Likely pathogenic ★ same condition
RORA p.Gln332_Tyr333insTer 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.Ile449Val Conflicting classifications of pathogenicity ★ ⚠ same residue
RORA p.Arg340fs Pathogenic/Likely pathogenic same condition
RORA p.Ala11Val 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-ile449fs (accessed [today's date]).

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