Is IL17RD p.Pro191= (c.573G>A) pathogenic?

IL17RD p.Pro191= (c.573G>A) is classified Likely benign in IL17RD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-25). Ultra-rare (popmax 0.0267%, eas).

How common is IL17RD p.Pro191= (c.573G>A) in the general population?

IL17RD p.Pro191= (c.573G>A) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

IL17RD p.Pro191=

c.573G>A · VCV4752240

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.1	GERP -5.8
Overall
CADD	4.147	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% East Asian · 12/44,862 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.0117% 189/1,611,950 alleles · ultra-rare exomes 163/1,459,828 · genomes 26/152,122 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.413%	242
Remaining individualsnot grpmax-eligible	0.0481%	2,081
East Asiangrpmax	0.0267%	3,738
South Asian	0.0022%	45,436
European (non-Finnish)	0.00187%	53,566
African / African-American	0.00133%	74,960

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: IL17RD
Protein: p.Pro191=
Coding: c.573G>A
MANE Select: NM_017563
Type: single nucleotide variant
Location: chr3:57106132 (GRCh38)
Gene constraint: LOEUF 0.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.68

Full IL17RD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IL17RD p.Pro191Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
IL17RD c.814-3C>T Uncertain significance ★★ same type
IL17RD p.Ala458Gly Uncertain significance ★★ ⚠ same type
IL17RD p.Arg203Gln Uncertain significance ★★ ⚠ same type
IL17RD p.Arg355Gln Uncertain significance ★★ ⚠ same type
IL17RD p.Asn19Ser Uncertain significance ★★ ⚠ same type
IL17RD p.Gln523His Uncertain significance ★★ ⚠ same type
IL17RD p.Gln563Arg 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/il17rd-p-pro191 (accessed [today's date]).

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