Is IL17RD p.Ser415Phe (c.1244C>T) pathogenic?

IL17RD p.Ser415Phe (c.1244C>T) is classified Uncertain significance in IL17RD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: likely pathogenic (0.8648); Very rare (popmax 0.0011%, sas).

How common is IL17RD p.Ser415Phe (c.1244C>T) in the general population?

IL17RD p.Ser415Phe (c.1244C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about IL17RD p.Ser415Phe (c.1244C>T)?

AlphaMissense predicts likely pathogenic (score 0.8648) — an in-silico prediction, not a clinical call.

IL17RD p.Ser415Phe

c.1244C>T · VCV4038222

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8648 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8648	likely pathogenic
REVEL	0.219	benign-leaning
SaProt	LLR -11.63	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 69 kb · p 0.026 · regional, not allelic
Overall
CADD	27.0	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 0.0011% South Asian · 1/91,080 alleles

Overall 6.2e-05% 1/1,613,966 alleles · very rare exomes 1/1,461,686 · genomes 0/152,280 · joint denominator

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.Ser415Phe
Coding: c.1244C>T
MANE Select: NM_017563
Type: single nucleotide variant
Location: chr3:57098459 (GRCh38)
Gene constraint: LOEUF 0.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.68
Residue 415: the sefir domain

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

Similar variants

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
IL17RD p.Glu239Lys 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-ser415phe (accessed [today's date]).

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