Is IL17RC p.Phe647Ser (c.1940T>C) pathogenic?

IL17RC p.Phe647Ser (c.1940T>C) is classified Uncertain significance in IL17RC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-04). AlphaMissense: likely pathogenic (0.9942); Very rare (popmax 0.00136%, nfe); Associated with candidiasis, familial, 9.

What condition is associated with IL17RC p.Phe647Ser (c.1940T>C)?

IL17RC p.Phe647Ser (c.1940T>C) is associated with candidiasis, familial, 9 (ClinVar).

How common is IL17RC p.Phe647Ser (c.1940T>C) in the general population?

IL17RC p.Phe647Ser (c.1940T>C) is very rare (popmax 0.00136%, 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.Phe647Ser (c.1940T>C)?

AlphaMissense predicts likely pathogenic (score 0.9942) — an in-silico prediction, not a clinical call.

IL17RC p.Phe647Ser

c.1940T>C · rs775185662 · VCV959863

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

candidiasis, familial, 9

Computational evidence

Protein change
AlphaMissense	0.9942	likely pathogenic · top 1% in IL17RC
REVEL	0.464	indeterminate
SaProt	LLR -9.56	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 16 kb · p 0.58 · regional, not allelic
Overall
CADD	27.1	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 F718S vs ClinVar F647S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,179,580 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00112% 18/1,612,562 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,550
Remaining individualsnot grpmax-eligible	0.0016%	62,384
European (non-Finnish)grpmax	0.00136%	73,724

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe647Ser
Coding: c.1940T>C
MANE Select: NM_153460
dbSNP: rs775185662
Type: single nucleotide variant
Location: chr3:9933370 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.19 · 5 PDB
Residue 647: the sefir domain

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-phe647ser (accessed [today's date]).

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