Is RORC p.Arg10Gln (c.29G>A) pathogenic?

RORC p.Arg10Gln (c.29G>A) is classified Uncertain significance in RORC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-05). AlphaMissense: likely benign (0.0913); Ultra-rare (popmax 0.0428%, sas); Associated with Inborn genetic diseases.

How common is RORC p.Arg10Gln (c.29G>A) in the general population?

RORC p.Arg10Gln (c.29G>A) is ultra-rare (popmax 0.0428%, sas) (gnomAD).

What do computational predictors say about RORC p.Arg10Gln (c.29G>A)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

RORC p.Arg10Gln

Q: What condition is associated with RORC p.Arg10Gln (c.29G>A)?

RORC p.Arg10Gln (c.29G>A) is associated with Inborn genetic diseases, autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (ClinVar).

c.29G>A · rs201874209 · VCV1368563

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0428%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -6.40	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 -2.3	GERP -2
Regional constraint	o/e 1.02	unconstrained · MANE · 2,316 bp · p 0.94 · regional, not allelic
Overall
CADD	15.01	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 0.0428% South Asian · 39/91,070 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0284%

Overall 0.00503% 81/1,610,620 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0428%	2,335
Middle Eastern	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0064%	15,615
Finnishnot grpmax-eligible	0.0033%	30,348
European (non-Finnish)	0.0028%	35,758
Admixed American	0.00167%	60,002
African / African-American	0.00133%	74,912

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.Arg10Gln
Coding: c.29G>A
MANE Select: NM_005060
dbSNP: rs201874209
Type: single nucleotide variant
Location: chr1:151831736 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 162 PDB
Residue 10: the 'modulating' region

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.Arg10Ter Conflicting classifications of pathogenicity ★ ⚠ same residue
RORC p.Arg10= Likely benign ★ same residue
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.Arg288Gln 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-arg10gln (accessed [today's date]).

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