Is RORA p.Pro30Gln (c.89C>A) pathogenic?

RORA p.Pro30Gln (c.89C>A) is classified Uncertain significance in RORA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.0896); Very rare (popmax 0.000524%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RORA p.Pro30Gln (c.89C>A)?

RORA p.Pro30Gln (c.89C>A) is associated with Inborn genetic diseases (ClinVar).

How common is RORA p.Pro30Gln (c.89C>A) in the general population?

RORA p.Pro30Gln (c.89C>A) is very rare (popmax 0.000524%, nfe) (gnomAD).

What do computational predictors say about RORA p.Pro30Gln (c.89C>A)?

AlphaMissense predicts likely benign (score 0.0896) — an in-silico prediction, not a clinical call.

RORA p.Pro30Gln

c.89C>A · VCV4156152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000524%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0896	likely benign
REVEL	0.458	indeterminate
SaProt	LLR -6.98	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 8.9	GERP 2.7, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 551 kb · p 0.0056 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000524% European (non-Finnish) · 6/1,144,846 alleles

Filtering AF 0.000189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000124%

Overall 0.000389% 6/1,542,788 alleles · very rare exomes 6/1,393,694 · genomes 0/149,094 · joint denominator

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.Pro30Gln
Coding: c.89C>A
MANE Select: NM_134261
Type: single nucleotide variant
Location: chr15:61229130 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.40 · 3 PDB
Residue 30: the 'disordered' region

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.Pro30= Likely benign ★★ same residue
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

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-pro30gln (accessed [today's date]).

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