Is RORA p.Arg340fs (c.1019del) pathogenic?

RORA p.Arg340fs (c.1019del) is classified Pathogenic/Likely pathogenic in RORA (ClinVar, No assertion criteria, 2 submitters; last evaluated 2018-07-27). Absent from gnomAD; Associated with Severe intellectual deficiency.

What condition is associated with RORA p.Arg340fs (c.1019del)?

RORA p.Arg340fs (c.1019del) is associated with Severe intellectual deficiency, intellectual developmental disorder with or without epilepsy or cerebellar ataxia (ClinVar).

How common is RORA p.Arg340fs (c.1019del) in the general population?

RORA p.Arg340fs (c.1019del) is absent from gnomAD (gnomAD).

RORA p.Arg340fs

c.1019del · rs1057518981 · VCV374220

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Severe intellectual deficiency

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 7 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.7	GERP 4.4, 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.Arg340fs
Coding: c.1019del
MANE Select: NM_134261
dbSNP: rs1057518981
Type: Deletion
Location: chr15:60503591 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.40 · 3 PDB
Residue 340: the nr lbd domain; an α-helix

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

Disease context

Severe intellectual deficiency

Also linked: intellectual developmental disorder with or without epilepsy or cerebellar ataxia

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 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.Arg340Cys Uncertain significance ★ ⚠ same residue
RORA p.Arg500Ter Pathogenic/Likely pathogenic ★★ 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-arg340fs (accessed [today's date]).

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