Is IL17A p.Arg95Pro (c.284G>C) pathogenic?

IL17A p.Arg95Pro (c.284G>C) is classified Uncertain significance in IL17A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely pathogenic (0.8852); Absent from gnomAD v4.1.

How common is IL17A p.Arg95Pro (c.284G>C) in the general population?

IL17A p.Arg95Pro (c.284G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IL17A p.Arg95Pro (c.284G>C)?

AlphaMissense predicts likely pathogenic (score 0.8852) — an in-silico prediction, not a clinical call.

IL17A p.Arg95Pro

c.284G>C · VCV4836275

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8852 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8852	likely pathogenic · top 10% in IL17A
REVEL	0.367	indeterminate
SaProt	LLR -12.37	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 2,857 bp · p 0.66 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: IL17A
Protein: p.Arg95Pro
Coding: c.284G>C
MANE Select: NM_002190
Type: single nucleotide variant
Location: chr6:52189108 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI 0.48 (gnomAD)
Structure: AlphaFold pLDDT 84.60 · 44 PDB
Residue 95: a β-strand

Full IL17A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IL17A c.27+18G>A Benign ★★ same type
IL17A p.Ala102Pro Uncertain significance ★ ⚠ same type
IL17A p.Arg134Trp Uncertain significance ★ ⚠ same type
IL17A p.Arg29Gly Uncertain significance ★ ⚠ same type
IL17A p.Arg69Gln Uncertain significance ★ ⚠ same type
IL17A p.Arg78His Uncertain significance ★ ⚠ same type
IL17A p.Asn101Ile Uncertain significance ★ ⚠ same type
IL17A p.Asn48Ile Uncertain significance ★ ⚠ same type

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/il17a-p-arg95pro (accessed [today's date]).

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