Is RORC p.Tyr330= (c.990C>T) pathogenic?

RORC p.Tyr330= (c.990C>T) is classified Benign/Likely benign in RORC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Rare (popmax 0.258%, nfe); Associated with autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency.

How common is RORC p.Tyr330= (c.990C>T) in the general population?

RORC p.Tyr330= (c.990C>T) is rare (popmax 0.258%, nfe) (gnomAD).

RORC p.Tyr330=

Q: What condition is associated with RORC p.Tyr330= (c.990C>T)?

RORC p.Tyr330= (c.990C>T) 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.990C>T · rs61754474 · VCV542379

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.258%, nfe)

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	<0.2	all four deltas below 0.2 · G>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.6	GERP -1.6
Overall
CADD	7.354	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.258% European (non-Finnish) · 3,046/1,179,974 alleles

Filtering AF 0.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.247%

Overall 0.222% 3,589/1,614,098 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.658%	152
Finnishnot grpmax-eligible	0.3%	334
European (non-Finnish)grpmax	0.258%	387
Remaining individualsnot grpmax-eligible	0.213%	470
Middle Eastern	0.115%	866
South Asian	0.102%	979
Admixed American	0.0766%	1,305
African / African-American	0.0533%	1,876
East Asian	0.0379%	2,640
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,290

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr330=
Coding: c.990C>T
MANE Select: NM_005060
dbSNP: rs61754474
Type: single nucleotide variant
Location: chr1:151813564 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 162 PDB
Residue 330: the nr lbd domain; an α-helix

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.Tyr330Ter Pathogenic ★ 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
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-tyr330 (accessed [today's date]).

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