Is RORC p.Arg3Lys (c.8G>A) pathogenic?

RORC p.Arg3Lys (c.8G>A) is classified Uncertain significance in RORC (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-03). AlphaMissense: likely benign (0.1615); No allele count reported in gnomAD v4.1 (AN 1,609,710); Associated with autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency.

How common is RORC p.Arg3Lys (c.8G>A) in the general population?

RORC p.Arg3Lys (c.8G>A) is no allele count reported in gnomAD v4.1 (AN 1,609,710) (gnomAD).

What do computational predictors say about RORC p.Arg3Lys (c.8G>A)?

AlphaMissense predicts likely benign (score 0.1615) — an in-silico prediction, not a clinical call.

RORC p.Arg3Lys

Q: What condition is associated with RORC p.Arg3Lys (c.8G>A)?

RORC p.Arg3Lys (c.8G>A) is associated with autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (ClinVar).

Q: How is Mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.8G>A · rs1652427545 · VCV844954

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1615 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,710)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.1615	likely benign
REVEL	0.478	indeterminate
SaProt	LLR -6.77	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 2.1	GERP 0.35, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 2,316 bp · p 0.94 · regional, not allelic
Overall
CADD	23.9	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

No allele count reported in gnomAD v4.1 (AN 1,609,710). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RORC
Protein: p.Arg3Lys
Coding: c.8G>A
MANE Select: NM_005060
dbSNP: rs1652427545
Type: single nucleotide variant
Location: chr1:151831757 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 162 PDB
Residue 3: the 'modulating' region

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

Disease context

autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

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.Arg288Gln Uncertain significance ★★ ⚠ same condition
RORC p.Arg82Gln Uncertain significance ★★ ⚠ same condition
RORC p.Asn373Ser 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-arg3lys (accessed [today's date]).

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