Is IL17F p.Pro48Ser (c.142C>T) pathogenic?

IL17F p.Pro48Ser (c.142C>T) is classified Uncertain significance in IL17F (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely benign (0.0938); Very rare (popmax 0.00223%, eas); Associated with candidiasis, familial, 6.

What condition is associated with IL17F p.Pro48Ser (c.142C>T)?

IL17F p.Pro48Ser (c.142C>T) is associated with candidiasis, familial, 6 (ClinVar).

How common is IL17F p.Pro48Ser (c.142C>T) in the general population?

IL17F p.Pro48Ser (c.142C>T) is very rare (popmax 0.00223%, 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 IL17F p.Pro48Ser (c.142C>T)?

AlphaMissense predicts likely benign (score 0.0938) — an in-silico prediction, not a clinical call.

IL17F p.Pro48Ser

c.142C>T · rs772268344 · VCV2722452

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0938 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

candidiasis, familial, 6

Computational evidence

Protein change
AlphaMissense	0.0938	likely benign
REVEL	0.36	indeterminate
SaProt	LLR -8.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,495 bp · p 0.7 · regional, not allelic
Overall
CADD	20.1	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,878 alleles

Overall 6.2e-05% 1/1,614,036 alleles · very rare exomes 1/1,461,764 · genomes 0/152,272 · joint denominator

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.Pro48Ser
Coding: c.142C>T
MANE Select: NM_052872
dbSNP: rs772268344
Type: single nucleotide variant
Location: chr6:52238842 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.75 · 9 PDB

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.Pro48Leu Uncertain significance ★ ⚠ same residue
IL17F p.Pro48= Likely benign ★ same residue
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

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-pro48ser (accessed [today's date]).

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