Is RORC p.Arg288Gln (c.863G>A) pathogenic?

RORC p.Arg288Gln (c.863G>A) is classified Uncertain significance in RORC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-19). AlphaMissense: likely benign (0.0797); Very rare (popmax 0.00161%, nfe); Associated with Inborn genetic diseases.

How common is RORC p.Arg288Gln (c.863G>A) in the general population?

RORC p.Arg288Gln (c.863G>A) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about RORC p.Arg288Gln (c.863G>A)?

AlphaMissense predicts likely benign (score 0.0797) — an in-silico prediction, not a clinical call.

RORC p.Arg288Gln

Q: What condition is associated with RORC p.Arg288Gln (c.863G>A)?

RORC p.Arg288Gln (c.863G>A) is associated with Inborn genetic diseases, autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (ClinVar).

c.863G>A · rs997157586 · VCV1501341

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0797 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0797	likely benign
REVEL	0.3	indeterminate
SaProt	LLR -6.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -0.4, phastCons 0.99
Regional constraint	o/e 0.52	unconstrained · MANE · 1,713 bp · p 5e-11 · regional, not allelic
Overall
CADD	20.5	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 0.00161% European (non-Finnish) · 19/1,179,340 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00118% 19/1,612,760 alleles · very rare exomes 19/1,460,480 · genomes 0/152,280 · 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: RORC
Protein: p.Arg288Gln
Coding: c.863G>A
MANE Select: NM_005060
dbSNP: rs997157586
Type: single nucleotide variant
Location: chr1:151814644 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 162 PDB
Residue 288: the nr lbd domain

Full RORC 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

Also linked: autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency

Similar variants

RORC p.Arg288= Likely benign ★★ same residue
RORC p.Arg288Trp Uncertain significance ★ ⚠ same residue
RORC p.Arg10Gln Uncertain significance ★★ ⚠ same condition
RORC p.Arg13Trp Uncertain significance ★★ ⚠ same condition
RORC p.Arg208Gln Uncertain significance ★★ ⚠ same condition
RORC p.Arg237Ser Uncertain significance ★★ ⚠ same condition
RORC p.Arg257His Uncertain significance ★★ ⚠ same condition
RORC p.Arg82Gln Uncertain significance ★★ ⚠ 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/rorc-p-arg288gln (accessed [today's date]).

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