Is IL17F p.Pro44Ser (c.130C>T) pathogenic?

IL17F p.Pro44Ser (c.130C>T) is classified Uncertain significance in IL17F (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-15). AlphaMissense: likely benign (0.0934); Very rare (popmax 8.48e-05%, nfe); Associated with candidiasis, familial, 6.

What condition is associated with IL17F p.Pro44Ser (c.130C>T)?

IL17F p.Pro44Ser (c.130C>T) is associated with candidiasis, familial, 6 (ClinVar).

How common is IL17F p.Pro44Ser (c.130C>T) in the general population?

IL17F p.Pro44Ser (c.130C>T) is very rare (popmax 8.48e-05%, 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 IL17F p.Pro44Ser (c.130C>T)?

AlphaMissense predicts likely benign (score 0.0934) — an in-silico prediction, not a clinical call.

IL17F p.Pro44Ser

c.130C>T · rs1331321771 · VCV2082611

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0934 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

candidiasis, familial, 6

Computational evidence

Protein change
AlphaMissense	0.0934	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -6.48	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 -0.18	GERP 0.47, phastCons 0.001
Regional constraint	o/e 0.97	unconstrained · MANE · 7,495 bp · p 0.7 · regional, not allelic
Overall
CADD	2.159	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 8.48e-05% European (non-Finnish) · 1/1,179,902 alleles

Overall 0.000124% 2/1,614,004 alleles · very rare exomes 2/1,461,736 · genomes 0/152,268 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
European (non-Finnish)grpmax	8.48e-05%	1,179,902

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: IL17F
Protein: p.Pro44Ser
Coding: c.130C>T
MANE Select: NM_052872
dbSNP: rs1331321771
Type: single nucleotide variant
Location: chr6:52238854 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.75 · 9 PDB
Residue 44: 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-pro44ser (accessed [today's date]).

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