Is RORA p.Glu329= (c.987A>G) pathogenic?

RORA p.Glu329= (c.987A>G) is classified Benign/Likely benign in RORA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-01). Low-frequency (popmax 1.28%, afr); Associated with intellectual developmental disorder with or without epilepsy or cerebellar ataxia.

How common is RORA p.Glu329= (c.987A>G) in the general population?

RORA p.Glu329= (c.987A>G) is low-frequency (popmax 1.28%, afr) (gnomAD).

RORA p.Glu329=

Q: What condition is associated with RORA p.Glu329= (c.987A>G)?

RORA p.Glu329= (c.987A>G) is associated with intellectual developmental disorder with or without epilepsy or cerebellar ataxia (ClinVar).

c.987A>G · rs141640548 · VCV782594

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.28%, afr)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 3.7, phastCons 1
Overall
CADD	10.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.28% African / African-American · 962/75,034 alleles

Filtering AF 1.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.19%

Overall 0.0665% 1,074/1,614,114 alleles · low-frequency exomes 505/1,461,818 · genomes 569/152,296 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.28%	78
Remaining individualsnot grpmax-eligible	0.088%	1,137
Admixed American	0.0816%	1,225
Middle Eastern	0.033%	3,030
South Asian	0.0022%	45,540
European (non-Finnish)	0.000339%	295,004

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RORA
Protein: p.Glu329=
Coding: c.987A>G
MANE Select: NM_134261
dbSNP: rs141640548
Type: single nucleotide variant
Location: chr15:60503623 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.40 · 3 PDB
Residue 329: 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-glu329 (accessed [today's date]).

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