Is RORC p.Ala63= (c.189G>A) pathogenic?

RORC p.Ala63= (c.189G>A) is classified Likely benign in RORC (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-11). Ultra-rare (popmax 0.0177%, sas); Associated with autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency.

How common is RORC p.Ala63= (c.189G>A) in the general population?

RORC p.Ala63= (c.189G>A) is ultra-rare (popmax 0.0177%, sas) (gnomAD).

RORC p.Ala63=

Q: What condition is associated with RORC p.Ala63= (c.189G>A)?

RORC p.Ala63= (c.189G>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.189G>A · rs778919253 · VCV1667313

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0177%, sas)

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -3.8, phastCons 1
Overall
CADD	14.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0177% South Asian · 15/84,516 alleles

Filtering AF 0.0109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00881%

Overall 0.00256% 40/1,564,760 alleles · ultra-rare exomes 38/1,412,552 · genomes 2/152,208 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0177%	5,634
Remaining individualsnot grpmax-eligible	0.00498%	20,069
East Asian	0.00231%	43,354
Admixed American	0.0018%	55,452
European (non-Finnish)	0.00174%	57,563

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.Ala63=
Coding: c.189G>A
MANE Select: NM_005060
dbSNP: rs778919253
Type: single nucleotide variant
Location: chr1:151816773 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 162 PDB
Residue 63: a DNA-binding 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.Ala63Thr Uncertain significance ★ ⚠ same residue
RORC p.Ala63Val Conflicting classifications of pathogenicity ★ ⚠ 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.Arg288Gln 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-ala63 (accessed [today's date]).

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