Is IL17RC p.Pro559fs (c.1674dup) pathogenic?

IL17RC p.Pro559fs (c.1674dup) is classified Conflicting classifications of pathogenicity in IL17RC (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2018-09-27). Very rare (popmax 8.58e-05%, nfe); Associated with candidiasis, familial, 9.

What condition is associated with IL17RC p.Pro559fs (c.1674dup)?

IL17RC p.Pro559fs (c.1674dup) is associated with candidiasis, familial, 9 (ClinVar).

How common is IL17RC p.Pro559fs (c.1674dup) in the general population?

IL17RC p.Pro559fs (c.1674dup) is very rare (popmax 8.58e-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.

IL17RC p.Pro559fs

c.1674dup · rs1559327071 · VCV624010

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.58e-05%, nfe)

Conditions

candidiasis, familial, 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (19 of 19) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.5	GERP 1.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.58e-05% European (non-Finnish) · 1/1,166,104 alleles

Overall 7.03e-05% 1/1,421,604 alleles · very rare

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.Pro559fs
Coding: c.1674dup
MANE Select: NM_153460
dbSNP: rs1559327071
Type: Duplication
Location: chr3:9933100 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.19 · 5 PDB

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 p.Pro559Ser Uncertain significance ★ ⚠ same residue
IL17RC c.1522+1dup Uncertain significance ★ same condition
IL17RC p.Ala480fs Uncertain significance ★ same condition
IL17RC p.Pro340_Leu341insPro Uncertain significance ★ same condition
IL17RC p.Ser282Ter Uncertain significance ★ same condition
IL17RC c.1522+19dup Likely benign ★ same condition
IL17RC c.356-16dup Likely benign ★ same condition
IL17RC c.105+146G>A 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-pro559fs (accessed [today's date]).

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