Is RORB p.Pro313Gln (c.938C>A) pathogenic?

RORB p.Pro313Gln (c.938C>A) is classified Uncertain significance in RORB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-22). AlphaMissense: ambiguous (0.5191); Very rare (popmax 8.48e-05%, nfe); Associated with epilepsy, idiopathic generalized, susceptibility to, 15.

What condition is associated with RORB p.Pro313Gln (c.938C>A)?

RORB p.Pro313Gln (c.938C>A) is associated with epilepsy, idiopathic generalized, susceptibility to, 15 (ClinVar).

How common is RORB p.Pro313Gln (c.938C>A) in the general population?

RORB p.Pro313Gln (c.938C>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about RORB p.Pro313Gln (c.938C>A)?

AlphaMissense predicts ambiguous (score 0.5191) — an in-silico prediction, not a clinical call.

RORB p.Pro313Gln

c.938C>A · rs2118526020 · VCV1526160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5191 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

epilepsy, idiopathic generalized, susceptibility to, 15

Computational evidence

Protein change
AlphaMissense	0.5191	ambiguous
REVEL	0.725	pathogenic-leaning
SaProt	LLR -10.86	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 20 kb · p 2.1e-06 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P324Q vs ClinVar P313Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,118 alleles

Overall 6.2e-05% 1/1,612,622 alleles · very rare exomes 1/1,460,424 · genomes 0/152,198 · 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: RORB
Protein: p.Pro313Gln
Coding: c.938C>A
MANE Select: NM_006914
dbSNP: rs2118526020
Type: single nucleotide variant
Location: chr9:74665533 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.48
Residue 324 UniProt numbering: the nr lbd domain; a UniProt-annotated variant site (in eig15; loss of subcellular location in the nucleoplasm)

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

Disease context

epilepsy, idiopathic generalized, susceptibility to, 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RORB c.94-1G>A Pathogenic/Likely pathogenic ★★ same condition
RORB p.Arg66Ter Pathogenic/Likely pathogenic ★★ same condition
RORB p.Phe33Leu Uncertain significance ★★ ⚠ same condition
RORB c.1225-9G>A Likely benign ★★ same condition
RORB p.Ile25= Benign/Likely benign ★★ same condition
RORB p.Leu118= Benign/Likely benign ★★ same condition
RORB c.1224+1G>T Likely pathogenic ★ same condition
RORB c.8-1G>A Likely pathogenic ★ 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/rorb-p-pro313gln (accessed [today's date]).

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