Is RORA p.Val390Ile (c.1168G>A) pathogenic?

RORA p.Val390Ile (c.1168G>A) is classified Likely benign in RORA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-06). AlphaMissense: likely benign (0.0769); Ultra-rare (popmax 0.024%, afr); Associated with Inborn genetic diseases.

What condition is associated with RORA p.Val390Ile (c.1168G>A)?

RORA p.Val390Ile (c.1168G>A) is associated with Inborn genetic diseases (ClinVar).

How common is RORA p.Val390Ile (c.1168G>A) in the general population?

RORA p.Val390Ile (c.1168G>A) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about RORA p.Val390Ile (c.1168G>A)?

AlphaMissense predicts likely benign (score 0.0769) — an in-silico prediction, not a clinical call.

RORA p.Val390Ile

c.1168G>A · VCV3790170

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0769 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0769	likely benign
REVEL	0.328	indeterminate
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 14 kb · p 1.2e-11 · regional, not allelic
Overall
CADD	16.31	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% African / African-American · 18/74,928 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00348% 56/1,611,400 alleles · ultra-rare exomes 45/1,459,168 · genomes 11/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,163
Admixed American	0.0167%	5,999
Remaining individualsnot grpmax-eligible	0.0144%	6,934
European (non-Finnish)	0.00161%	61,981

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.Val390Ile
Coding: c.1168G>A
MANE Select: NM_134261
Type: single nucleotide variant
Location: chr15:60502775 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.40 · 3 PDB
Residue 390: the nr lbd domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RORA p.Arg462Ter Pathogenic/Likely pathogenic ★★ same condition
RORA p.Ala7Ser Uncertain significance ★★ ⚠ same condition
RORA p.Gln278His Uncertain significance ★★ ⚠ same condition
RORA p.Gly211Arg Uncertain significance ★★ ⚠ same condition
RORA p.Lys151Gln Uncertain significance ★★ ⚠ same condition
RORA p.Thr328Arg Uncertain significance ★★ ⚠ same condition
RORA c.197-26379G>A Likely benign ★★ same condition
RORA p.Asp21Gly Likely benign ★★ 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-val390ile (accessed [today's date]).

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