Is IL17RC p.Pro63Arg (c.188C>G) pathogenic?

IL17RC p.Pro63Arg (c.188C>G) is classified Uncertain significance in IL17RC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-12). AlphaMissense: likely pathogenic (0.869); Very rare (popmax 8.47e-05%, nfe); Associated with candidiasis, familial, 9.

What condition is associated with IL17RC p.Pro63Arg (c.188C>G)?

IL17RC p.Pro63Arg (c.188C>G) is associated with candidiasis, familial, 9 (ClinVar).

How common is IL17RC p.Pro63Arg (c.188C>G) in the general population?

IL17RC p.Pro63Arg (c.188C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Chronic mucocutaneous candidiasis inherited?

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

What do computational predictors say about IL17RC p.Pro63Arg (c.188C>G)?

AlphaMissense predicts likely pathogenic (score 0.869) — an in-silico prediction, not a clinical call.

IL17RC p.Pro63Arg

c.188C>G · rs2083243386 · VCV2022129

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.869 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

candidiasis, familial, 9

Computational evidence

Protein change
AlphaMissense	0.869	likely pathogenic · top 7% in IL17RC
REVEL	0.242	benign-leaning
SaProt	LLR -14.39	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 16 kb · p 0.58 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P134R vs ClinVar P63R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,968 alleles

Overall 6.2e-05% 1/1,613,886 alleles · very rare exomes 1/1,461,532 · genomes 0/152,354 · joint denominator

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: IL17RC
Protein: p.Pro63Arg
Coding: c.188C>G
MANE Select: NM_153460
dbSNP: rs2083243386
Type: single nucleotide variant
Location: chr3:9917983 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.19 · 5 PDB
Residue 134 UniProt numbering: a β-strand

Full IL17RC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

candidiasis, familial, 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Chronic mucocutaneous candidiasis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood, Infancy

Similar variants

IL17RC c.105+146G>A Uncertain significance ★★ ⚠ same condition
IL17RC c.105+25G>A Uncertain significance ★★ ⚠ same condition
IL17RC c.105+33G>T Uncertain significance ★★ ⚠ same condition
IL17RC c.106-144G>A Uncertain significance ★★ ⚠ same condition
IL17RC p.Ala166Val Uncertain significance ★★ ⚠ same condition
IL17RC p.Ala30Ser Uncertain significance ★★ ⚠ same condition
IL17RC p.Ala326Thr Uncertain significance ★★ ⚠ same condition
IL17RC p.Ala480Val 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/il17rc-p-pro63arg (accessed [today's date]).

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