Is IDE p.Ser484Ala (c.1450T>G) pathogenic?

IDE p.Ser484Ala (c.1450T>G) is classified Uncertain significance in IDE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-02). AlphaMissense: likely benign (0.096); Very rare (popmax 0.00834%, amr).

How common is IDE p.Ser484Ala (c.1450T>G) in the general population?

IDE p.Ser484Ala (c.1450T>G) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about IDE p.Ser484Ala (c.1450T>G)?

AlphaMissense predicts likely benign (score 0.096) — an in-silico prediction, not a clinical call.

IDE p.Ser484Ala

c.1450T>G · rs149596491 · VCV3108007

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.096 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.096	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -8.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 56 kb · p 4.3e-15 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00834% Admixed American · 5/59,946 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000807% 13/1,610,276 alleles · very rare exomes 10/1,458,064 · genomes 3/152,212 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,989
Remaining individualsnot grpmax-eligible	0.0016%	62,326
African / African-American	0.00134%	74,832
European (non-Finnish)	0.00051%	196,128

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: IDE
Protein: p.Ser484Ala
Coding: c.1450T>G
MANE Select: NM_004969
dbSNP: rs149596491
Type: single nucleotide variant
Location: chr10:92490576 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 62 PDB
Residue 484: an α-helix

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

Similar variants

IDE p.Asn841= Benign ★★ same type
IDE p.His10= Benign/Likely benign ★★ same type
IDE p.Ile791= Benign ★★ same type
IDE p.Ala185Glu Uncertain significance ★ ⚠ same type
IDE p.Ala452Thr Uncertain significance ★ ⚠ same type
IDE p.Ala479Thr Uncertain significance ★ ⚠ same type
IDE p.Ala544Val Uncertain significance ★ ⚠ same type
IDE p.Ala610Val 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/ide-p-ser484ala (accessed [today's date]).

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