Is IL17A p.Arg134= (c.402G>A) pathogenic?

IL17A p.Arg134= (c.402G>A) is classified Benign in IL17A (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-27). Common (popmax 6%, afr) — too common for a highly-penetrant pathogenic allele.

IL17A p.Arg134=

Q: How common is IL17A p.Arg134= (c.402G>A) in the general population?

IL17A p.Arg134= (c.402G>A) is common (popmax 6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.402G>A · rs17880588 · VCV771398

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 6%, afr) — too common for a highly-penetrant pathogenic allele

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 0.19	GERP -0.91
Overall
CADD	4.071	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6% African / African-American · 4,502/75,000 alleles

Filtering AF 5.86% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.8%

Overall 0.334% 5,387/1,614,082 alleles · common exomes 2,834/1,461,812 · genomes 2,553/152,270 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6%	17
Middle Eastern	0.924%	108
Remaining individualsnot grpmax-eligible	0.504%	198
Admixed American	0.485%	206
South Asian	0.0406%	2,462
European (non-Finnish)	0.0158%	6,344

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: IL17A
Protein: p.Arg134=
Coding: c.402G>A
MANE Select: NM_002190
dbSNP: rs17880588
Type: single nucleotide variant
Location: chr6:52189226 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI 0.48 (gnomAD)
Structure: AlphaFold pLDDT 84.60 · 44 PDB

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

Similar variants

IL17A p.Arg134Trp Uncertain significance ★ ⚠ same residue
IL17A c.27+18G>A Benign ★★ same type
IL17A p.Ala102Pro 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.Arg95Pro Uncertain significance ★ ⚠ same type
IL17A p.Asn101Ile 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-arg134 (accessed [today's date]).

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