Is RORA p.Ala358Thr (c.1072G>A) pathogenic?

RORA p.Ala358Thr (c.1072G>A) is classified Uncertain significance in RORA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-01). AlphaMissense: ambiguous (0.5396); Absent from gnomAD v4.1.

How common is RORA p.Ala358Thr (c.1072G>A) in the general population?

RORA p.Ala358Thr (c.1072G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RORA p.Ala358Thr (c.1072G>A)?

AlphaMissense predicts ambiguous (score 0.5396) — an in-silico prediction, not a clinical call.

RORA p.Ala358Thr

c.1072G>A · rs2141276372 · VCV1310282

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5396 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5396	ambiguous
REVEL	0.624	indeterminate
SaProt	LLR -9.83	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 5, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 14 kb · p 1.2e-11 · regional, not allelic
Overall
CADD	26.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RORA
Protein: p.Ala358Thr
Coding: c.1072G>A
MANE Select: NM_134261
dbSNP: rs2141276372
Type: single nucleotide variant
Location: chr15:60503538 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.40 · 3 PDB
Residue 358: the nr lbd domain; an α-helix

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.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
RORA p.Gln278His 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-ala358thr (accessed [today's date]).

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