Is RORC p.Val28Gly (c.83T>G) pathogenic?

RORC p.Val28Gly (c.83T>G) is classified Uncertain significance in RORC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-10). AlphaMissense: likely pathogenic (0.6206); Absent from gnomAD v4.1; Associated with autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency.

How common is RORC p.Val28Gly (c.83T>G) in the general population?

RORC p.Val28Gly (c.83T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RORC p.Val28Gly (c.83T>G)?

AlphaMissense predicts likely pathogenic (score 0.6206) — an in-silico prediction, not a clinical call.

RORC p.Val28Gly

Q: What condition is associated with RORC p.Val28Gly (c.83T>G)?

RORC p.Val28Gly (c.83T>G) 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.83T>G · rs2101662490 · VCV1365476

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6206 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.6206	likely pathogenic
REVEL	0.712	pathogenic-leaning
SaProt	LLR -13.96	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 13 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RORC
Protein: p.Val28Gly
Coding: c.83T>G
MANE Select: NM_005060
dbSNP: rs2101662490
Type: single nucleotide variant
Location: chr1:151817268 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 162 PDB
Residue 28: 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-val28gly (accessed [today's date]).

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