Is IDE p.Pro461Ala (c.1381C>G) pathogenic?

IDE p.Pro461Ala (c.1381C>G) is classified Uncertain significance in IDE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.2077); Absent from gnomAD v4.1.

How common is IDE p.Pro461Ala (c.1381C>G) in the general population?

IDE p.Pro461Ala (c.1381C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IDE p.Pro461Ala (c.1381C>G)?

AlphaMissense predicts likely benign (score 0.2077) — an in-silico prediction, not a clinical call.

IDE p.Pro461Ala

c.1381C>G · rs747481660 · VCV2491328

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2077 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2077	likely benign
REVEL	0.261	benign-leaning
SaProt	LLR -9.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 0.87, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 56 kb · p 4.3e-15 · regional, not allelic
Overall
CADD	25.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IDE
Protein: p.Pro461Ala
Coding: c.1381C>G
MANE Select: NM_004969
dbSNP: rs747481660
Type: single nucleotide variant
Location: chr10:92504843 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 62 PDB
Residue 461: an α-helix

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

Similar variants

IDE p.Pro461Ser Uncertain significance ★ ⚠ same residue
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

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-pro461ala (accessed [today's date]).

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