Is RORC p.Arg288Trp (c.862C>T) pathogenic?

RORC p.Arg288Trp (c.862C>T) is classified Uncertain significance in RORC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-06). AlphaMissense: likely benign (0.1191); Very rare (popmax 0.00133%, afr).

How common is RORC p.Arg288Trp (c.862C>T) in the general population?

RORC p.Arg288Trp (c.862C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about RORC p.Arg288Trp (c.862C>T)?

AlphaMissense predicts likely benign (score 0.1191) — an in-silico prediction, not a clinical call.

RORC p.Arg288Trp

c.862C>T · VCV4911040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1191 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1191	likely benign
REVEL	0.6	indeterminate
SaProt	LLR -12.32	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP -0.44, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 1,713 bp · p 5e-11 · regional, not allelic
Overall
CADD	24.5	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

Grpmax group 0.00133% African / African-American · 1/75,032 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,612,632 alleles · very rare exomes 3/1,460,336 · genomes 0/152,296 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,032
European (non-Finnish)	0.00017%	589,637

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.Arg288Trp
Coding: c.862C>T
MANE Select: NM_005060
Type: single nucleotide variant
Location: chr1:151814645 (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

Similar variants

RORC p.Arg288Gln Uncertain significance ★★ ⚠ same residue
RORC p.Arg288= Likely benign ★★ same residue
RORC p.Arg10Gln Uncertain significance ★★ ⚠ same type
RORC p.Arg13Trp Uncertain significance ★★ ⚠ same type
RORC p.Arg208Gln Uncertain significance ★★ ⚠ same type
RORC p.Arg237Ser Uncertain significance ★★ ⚠ same type
RORC p.Arg257His Uncertain significance ★★ ⚠ same type
RORC p.Arg82Gln 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/rorc-p-arg288trp (accessed [today's date]).

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