Is RORB p.Arg214Gln (c.641G>A) pathogenic?

RORB p.Arg214Gln (c.641G>A) is classified Uncertain significance in RORB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-24). AlphaMissense: likely benign (0.0997); Very rare (popmax 0.00402%, afr); Associated with Inborn genetic diseases.

What condition is associated with RORB p.Arg214Gln (c.641G>A)?

RORB p.Arg214Gln (c.641G>A) is associated with Inborn genetic diseases (ClinVar).

How common is RORB p.Arg214Gln (c.641G>A) in the general population?

RORB p.Arg214Gln (c.641G>A) is very rare (popmax 0.00402%, afr) (gnomAD).

What do computational predictors say about RORB p.Arg214Gln (c.641G>A)?

AlphaMissense predicts likely benign (score 0.0997) — an in-silico prediction, not a clinical call.

RORB p.Arg214Gln

c.641G>A · rs1824166411 · VCV2332276

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0997 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0997	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -4.14	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 10	GERP 2.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 18 kb · p 0.076 · regional, not allelic
Overall
CADD	25.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R225Q vs ClinVar R214Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00402% African / African-American · 3/74,642 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000373% 6/1,607,902 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00402%	24,881
South Asian	0.00112%	89,514
European (non-Finnish)	0.00017%	589,095

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.Arg214Gln
Coding: c.641G>A
MANE Select: NM_006914
dbSNP: rs1824166411
Type: single nucleotide variant
Location: chr9:74660620 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.48
Residue 214: 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

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

Similar variants

RORB p.Arg214Ter Pathogenic/Likely pathogenic ★★ same residue
RORB p.Ala95Thr Uncertain significance ★★ ⚠ same condition
RORB p.Asp337Glu Uncertain significance ★★ ⚠ same condition
RORB p.Gln107Arg Uncertain significance ★★ ⚠ same condition
RORB p.Ile147Thr Uncertain significance ★★ ⚠ same condition
RORB p.Ile183Val Uncertain significance ★★ ⚠ same condition
RORB p.Pro205Ser Likely benign ★★ same condition
RORB p.Cys10Ter 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-arg214gln (accessed [today's date]).

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