Is IL17F p.Ile74= (c.222C>T) pathogenic?

IL17F p.Ile74= (c.222C>T) is classified Benign/Likely benign in IL17F (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-28). Rare (popmax 0.466%, afr); Associated with candidiasis, familial, 6.

What condition is associated with IL17F p.Ile74= (c.222C>T)?

IL17F p.Ile74= (c.222C>T) is associated with candidiasis, familial, 6 (ClinVar).

How common is IL17F p.Ile74= (c.222C>T) in the general population?

IL17F p.Ile74= (c.222C>T) is rare (popmax 0.466%, afr) (gnomAD).

How is Chronic mucocutaneous candidiasis inherited?

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

IL17F p.Ile74=

c.222C>T · rs6931727 · VCV471811

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.466%, afr)

Conditions

candidiasis, familial, 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.22	GERP -1.8, phastCons 0.9
Overall
CADD	7.316	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.466% African / African-American · 350/75,050 alleles

Filtering AF 0.426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.41%

Overall 0.0277% 447/1,614,156 alleles · rare exomes 222/1,461,852 · genomes 225/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.466%	214
Admixed American	0.09%	1,112
Remaining individualsnot grpmax-eligible	0.0512%	1,953
Middle Eastern	0.0165%	6,062
East Asian	0.00223%	44,882
South Asian	0.0011%	91,084
European (non-Finnish)	0.000678%	147,501

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: IL17F
Protein: p.Ile74=
Coding: c.222C>T
MANE Select: NM_052872
dbSNP: rs6931727
Type: single nucleotide variant
Location: chr6:52238762 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.75 · 9 PDB
Residue 74: an α-helix

Full IL17F gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

candidiasis, familial, 6 — 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

IL17F p.Ala23Pro Uncertain significance ★★ ⚠ same condition
IL17F p.Arg131Gln Uncertain significance ★★ ⚠ same condition
IL17F p.Arg67His Uncertain significance ★★ ⚠ same condition
IL17F p.Arg72Cys Uncertain significance ★★ ⚠ same condition
IL17F p.Arg92Gln Uncertain significance ★★ same condition
IL17F p.Asn63Ser Uncertain significance ★★ ⚠ same condition
IL17F p.Asp115Glu Uncertain significance ★★ ⚠ same condition
IL17F p.Gln135Glu 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/il17f-p-ile74 (accessed [today's date]).

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