Is IL17RC p.Pro699Ser (c.2095C>T) pathogenic?

IL17RC p.Pro699Ser (c.2095C>T) is classified Uncertain significance in IL17RC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-19). AlphaMissense: likely benign (0.0823); Absent from gnomAD v4.1; Associated with candidiasis, familial, 9.

What condition is associated with IL17RC p.Pro699Ser (c.2095C>T)?

IL17RC p.Pro699Ser (c.2095C>T) is associated with candidiasis, familial, 9 (ClinVar).

How common is IL17RC p.Pro699Ser (c.2095C>T) in the general population?

IL17RC p.Pro699Ser (c.2095C>T) is absent from gnomAD v4.1 (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.Pro699Ser (c.2095C>T)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

IL17RC p.Pro699Ser

c.2095C>T · VCV3642125

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

candidiasis, familial, 9

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -7.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.63	GERP -2.2
Regional constraint	o/e 1.02	unconstrained · MANE · 16 kb · p 0.58 · regional, not allelic
Overall
CADD	6.984	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P770S vs ClinVar P699S) — verify the residue.

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: IL17RC
Protein: p.Pro699Ser
Coding: c.2095C>T
MANE Select: NM_153460
Type: single nucleotide variant
Location: chr3:9933525 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.19 · 5 PDB
Residue 770 UniProt numbering: the 'disordered' region

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.Pro699Leu Uncertain significance ★ ⚠ same residue
IL17RC p.Pro699= 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-pro699ser (accessed [today's date]).

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