Is IL17RC p.Pro59Ser (c.175C>T) pathogenic?

IL17RC p.Pro59Ser (c.175C>T) is classified Uncertain significance in IL17RC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-27). AlphaMissense: ambiguous (0.5144); Very rare (popmax 0.00446%, eas); Associated with candidiasis, familial, 9.

What condition is associated with IL17RC p.Pro59Ser (c.175C>T)?

IL17RC p.Pro59Ser (c.175C>T) is associated with candidiasis, familial, 9 (ClinVar).

How common is IL17RC p.Pro59Ser (c.175C>T) in the general population?

IL17RC p.Pro59Ser (c.175C>T) is very rare (popmax 0.00446%, eas) (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.Pro59Ser (c.175C>T)?

AlphaMissense predicts ambiguous (score 0.5144) — an in-silico prediction, not a clinical call.

IL17RC p.Pro59Ser

c.175C>T · rs753283137 · VCV661489

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5144 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

candidiasis, familial, 9

Computational evidence

Protein change
AlphaMissense	0.5144	ambiguous
REVEL	0.272	benign-leaning
SaProt	LLR -9.64	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
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	23.6	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 P130S vs ClinVar P59S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,882 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000274% 4/1,461,440 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,441
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	8.47e-05%	1,180,002

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.Pro59Ser
Coding: c.175C>T
MANE Select: NM_153460
dbSNP: rs753283137
Type: single nucleotide variant
Location: chr3:9917970 (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.Pro59Ala Uncertain significance ★★ ⚠ same residue
IL17RC p.Pro59= Likely benign ★ same residue
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

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-pro59ser (accessed [today's date]).

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