Is RORA p.Ala24Thr (c.70G>A) pathogenic?

RORA p.Ala24Thr (c.70G>A) is classified Uncertain significance in RORA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-01). AlphaMissense: likely benign (0.0814); Very rare (popmax 8.73e-05%, nfe).

How common is RORA p.Ala24Thr (c.70G>A) in the general population?

RORA p.Ala24Thr (c.70G>A) is very rare (popmax 8.73e-05%, nfe) (gnomAD).

What do computational predictors say about RORA p.Ala24Thr (c.70G>A)?

AlphaMissense predicts likely benign (score 0.0814) — an in-silico prediction, not a clinical call.

RORA p.Ala24Thr

c.70G>A · VCV3905923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0814 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.73e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0814	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -8.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.64, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 551 kb · p 0.0056 · regional, not allelic
Overall
CADD	16.84	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 8.73e-05% European (non-Finnish) · 1/1,145,544 alleles

Overall 6.48e-05% 1/1,544,096 alleles · very rare exomes 1/1,395,030 · genomes 0/149,066 · 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.Ala24Thr
Coding: c.70G>A
MANE Select: NM_134261
Type: single nucleotide variant
Location: chr15:61229149 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.40 · 3 PDB
Residue 24: the 'disordered' region

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

Similar variants

RORA p.Arg462Ter Pathogenic/Likely pathogenic ★★ same type
RORA p.Arg500Ter Pathogenic/Likely pathogenic ★★ same type
RORA p.Ala11Val Uncertain significance ★★ ⚠ same type
RORA p.Ala358Thr Uncertain significance ★★ same type
RORA p.Ala7Ser Uncertain significance ★★ ⚠ same type
RORA p.Arg170His Uncertain significance ★★ ⚠ same type
RORA p.Arg462Gln Uncertain significance ★★ ⚠ same type
RORA p.Arg47Thr Uncertain significance ★★ same type

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-ala24thr (accessed [today's date]).

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