Is IDE p.Pro343Ser (c.1027C>T) pathogenic?

IDE p.Pro343Ser (c.1027C>T) is classified Uncertain significance in IDE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-07). AlphaMissense: ambiguous (0.4525); Very rare (popmax 0.000424%, nfe).

How common is IDE p.Pro343Ser (c.1027C>T) in the general population?

IDE p.Pro343Ser (c.1027C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about IDE p.Pro343Ser (c.1027C>T)?

AlphaMissense predicts ambiguous (score 0.4525) — an in-silico prediction, not a clinical call.

IDE p.Pro343Ser

c.1027C>T · VCV3527484

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4525 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4525	ambiguous
REVEL	0.434	indeterminate
SaProt	LLR -5.71	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 56 kb · p 4.3e-15 · regional, not allelic
Overall
CADD	25.3	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 0.000424% European (non-Finnish) · 5/1,179,998 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,944 alleles · very rare exomes 4/1,461,832 · genomes 1/152,112 · 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: IDE
Protein: p.Pro343Ser
Coding: c.1027C>T
MANE Select: NM_004969
Type: single nucleotide variant
Location: chr10:92508761 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 62 PDB

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-pro343ser (accessed [today's date]).

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