Is IL17RD p.Pro3Ser (c.7C>T) pathogenic?

IL17RD p.Pro3Ser (c.7C>T) is classified Uncertain significance in IL17RD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: ambiguous (0.3732); Very rare (popmax 0.00238%, amr).

How common is IL17RD p.Pro3Ser (c.7C>T) in the general population?

IL17RD p.Pro3Ser (c.7C>T) is very rare (popmax 0.00238%, amr) (gnomAD).

What do computational predictors say about IL17RD p.Pro3Ser (c.7C>T)?

AlphaMissense predicts ambiguous (score 0.3732) — an in-silico prediction, not a clinical call.

IL17RD p.Pro3Ser

c.7C>T · VCV4678491

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3732 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00238%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3732	ambiguous
REVEL	0.158	moderately benign-leaning
SaProt	LLR -5.58	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.1, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 69 kb · p 0.026 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00238% Admixed American · 1/42,012 alleles

Filtering AF 0.000262% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000168%

Overall 0.000541% 8/1,478,910 alleles · very rare exomes 6/1,327,002 · genomes 2/151,908 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00238%	42,012
European (non-Finnish)	0.000629%	159,033

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.Pro3Ser
Coding: c.7C>T
MANE Select: NM_017563
Type: single nucleotide variant
Location: chr3:57165280 (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.Pro3Arg Uncertain significance ★ ⚠ 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-pro3ser (accessed [today's date]).

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