Is IL17RA p.Leu826Val (c.2476C>G) pathogenic?

IL17RA p.Leu826Val (c.2476C>G) is classified Uncertain significance in IL17RA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-25). AlphaMissense: likely benign (0.066); Absent from gnomAD v4.1; Associated with immunodeficiency 51.

What condition is associated with IL17RA p.Leu826Val (c.2476C>G)?

IL17RA p.Leu826Val (c.2476C>G) is associated with immunodeficiency 51 (ClinVar).

How common is IL17RA p.Leu826Val (c.2476C>G) in the general population?

IL17RA p.Leu826Val (c.2476C>G) 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 IL17RA p.Leu826Val (c.2476C>G)?

AlphaMissense predicts likely benign (score 0.066) — an in-silico prediction, not a clinical call.

IL17RA p.Leu826Val

c.2476C>G · rs1568924494 · VCV571940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.066 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 51

Computational evidence

Protein change
AlphaMissense	0.066	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.14	GERP -2.6
Regional constraint	o/e 1.09	unconstrained · MANE · 25 kb · p 0.0019 · regional, not allelic
Overall
CADD	0.079	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

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: IL17RA
Protein: p.Leu826Val
Coding: c.2476C>G
MANE Select: NM_014339
dbSNP: rs1568924494
Type: single nucleotide variant
Location: chr22:17109695 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.33 · 10 PDB
Residue 826: a UniProt-annotated variant site (in imd51; results in complete loss of expression and loss-of-function); the 'disordered' region

Full IL17RA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 51 — 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

IL17RA p.Leu826= Likely benign ★ same residue
IL17RA p.Arg66Ter Pathogenic/Likely pathogenic ★★ same condition
IL17RA c.598+5C>T Uncertain significance ★★ same condition
IL17RA c.*2141C>T Uncertain significance ★★ same condition
IL17RA p.Ala299Thr Uncertain significance ★★ ⚠ same condition
IL17RA p.Ala3Val Uncertain significance ★★ ⚠ same condition
IL17RA p.Ala419Gly Uncertain significance ★★ ⚠ same condition
IL17RA p.Ala463Thr 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/il17ra-p-leu826val (accessed [today's date]).

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