Is RORC p.Glu303fs (c.908del) pathogenic?

RORC p.Glu303fs (c.908del) is classified Pathogenic in RORC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-02). Associated with autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency.

RORC p.Glu303fs

Q: What condition is associated with RORC p.Glu303fs (c.908del)?

RORC p.Glu303fs (c.908del) 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.908del · VCV3722087

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 6 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -0.38, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: RORC
Protein: p.Glu303fs
Coding: c.908del
MANE Select: NM_005060
Type: Deletion
Location: chr1:151814599 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 162 PDB
Residue 303: 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.Arg69fs Pathogenic ★ same condition
RORC c.821_933+84del Uncertain significance ★ same condition
RORC c.1174+9del Likely benign ★ same condition
RORC c.298+16_298+17del Likely benign ★ same condition
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

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-glu303fs (accessed [today's date]).

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